Patent Application
20250177965
The disclosed invention is generally in the field of heterogeneous catalysts which can be used, for example, in cycloaddition reactions.
Construction of aryl-substituted cyclobutane rings, the prominent structural features in a vast array of bioactive molecules (Goetzke, F. W., Hell, A. M. L., van Dijk, L. & Fletcher, S. P. A catalytic asymmetric cross-coupling approach to the synthesis of cyclobutanes. Nat. Chem. 13, 880-886 (2021); Dembitsky, V. M. Naturally occurring bioactive cyclobutane-containing (CBC) alkaloids in fungi, fungal endophytes, and plants. Phytomedicine 21, 1559-1581 (2014)), is essential for natural product synthesis and drug discovery (Namyslo, J. C. & Kaufmann, D. E. The application of cyclobutane derivatives in organic synthesis. Chem. Rev. 103, 1485-1538 (2003); Wang, M. & Lu, P. Catalytic approaches to assemble cyclobutane motifs in natural product synthesis. Org. Chem. Front. 5, 254-259 (2018)).
Photochemical [2+2]cycloadditions are arguably the most straightforward way to prepare such cyclobutane-containing compounds, and rely primarily on the activation of styrenes via electron or energy transfer with transition-metal or organic photosensitizers (Poplata, S., Tröster, A., Zou, Y.-Q. & Bach, T. Recent advances in the synthesis of cyclobutanes by olefin [2+2] photocycloaddition reactions. Chem. Rev. 116, 9748-9815 (2016); Zhou, Q.-Q., Zou, Y.-Q., Lu, L.-Q. & Xiao, W.-J. Visible-light-induced organic photochemical reactions through energy-transfer pathways. Angew. Chem. Int. Ed. 58, 1586-1604 (2019); Sicignano, M., Rodríguez, R. I. & Alemán, J. Recent visible light and metal free strategies in [2+2] and [4+2]photocycloadditions. Eur. J. Org. Chem. 2021, 3303-3321 (2021); Zhu, M., Zhang, X., Zheng, C. & You, S.-L. Energy-transfer-enabled dearomative cycloaddition reactions of indoles/pyrroles via excited-state aromatics. Acc. Chem. Res. 55, 2510-2525 (2022)). The same type of oxidative intermolecular crossed [2+2]cycloadditions have also been achieved using various polymer-based heterogeneous photocatalysts (Li, R. et al. Photocatalytic regioselective and stereoselective [2+2]cycloaddition of styrene derivatives using a heterogeneous organic photocatalyst. ACS Catal. 7, 3097-3101 (2017); Piane, J. J. et al. Organic photoredox-catalyzed cycloadditions under single-chain polymer confinement. ACS Catal. 10, 13251-13256 (2020)). While the Yoon group reported the first intramolecular crossed [2+2]cycloadditions of 1,2-disubstituted styrenes through triplet-energy-transfer catalysis in 2012(Lu, Z. & Yoon, T. P. Visible light photocatalysis of [2+2] styrene cycloadditions by energy transfer. Angew. Chem. Int. Ed. 51, 10329-10332 (2012)), intermolecular [2+2]cycloadditions between different styrenes involving triplet styrene formation were not realized until very recently(Liu, Z. et al. Aggregation-enabled intermolecular photo[2+2]cycloaddition of aryl terminal olefins by visible-light catalysis. CCS Chem. 2, 582-588 (2020)). In terms of heterogeneous photocatalytic energy transfer, only quantum dots are reported to be capable of promoting styrene [2+2]cycloadditions (Jiang, Y., Wang, C., Rogers, C. R., Kodaimati, M. S. & Weiss, E. A. Regio- and diastereoselective intermolecular [2+2]cycloadditions photocatalysed by quantum dots. Nat. Chem. 11, 1034-1040 (2019))..
Despite substantial advances in triplet photosensitization over the past decades, developing intermolecular crossed [2+2]cycloadditions of simple styrenes with other alkenes still remains a significant challenge using visible light photocatalysis.
Accordingly, there remains a need for improved catalysts which can address the aforementioned issues for use in cycloaddition reactions.
Therefore, it is an object of the present invention to provide heterogeneous catalysts with improved properties.
It is a further object of the present invention to provide methods of making such heterogeneous catalysts.
It is still a further object of the present invention to provide methods of using such heterogeneous catalysts to efficiently drive cycloaddition reactions.
Heterogeneous catalysts which can be used in chemical reactions, such as [2+2]cycloadditions are described herein. In one instance, a non-limiting example a heterogenous catalyst includes:
In certain instances, the catalyst complex within the metal-organic framework includes a chemical structure as follows:
where the wavy bonds extending from the phenanthroline moiety are understood by the skilled artisan to be part of an organic linker containing the moiety within the metal-organic framework.
The heterogeneous catalysts (i.e., heteroleptic copper(I) complexes with bidentate nitrogen and phosphorus donor ligands) function as photoredox catalysts and (high) triplet photosensitizers, which can be used for a wide range of light-mediated organic transformations. The heterogeneous catalysts can provide high turnover numbers (TON) in a range of about 50 to 5000 turnovers, as well as sub-ranges or individual values contained within the aforementioned range.
The heterogeneous catalysts typically have relatively long photoexcited-state lifetimes. For instance, the heterogeneous catalysts can have an excited-state lifetime at room temperature of at least about 3, 3.5, 4, 4.5, or 5 μs; or an excited-state lifetime at room temperature in a range of between about 3 to 5 μs, as well as sub-ranges or individual values contained within the aforementioned range.
The heterogeneous catalysts described can be synthesized by various methods. In one instance, a non-limiting method of synthesizing a heterogenous catalyst includes the steps of:
In another non-limiting instance, a method of synthesizing a heterogenous catalyst includes the steps of:
The heterogeneous catalysts described below can be used in large-scale synthesis and demonstrate catalyst recyclability, as well as facilitate the separation of catalyst and product. Moreover, the heterogeneous catalysts can be employed to achieve organic transformations that are not known to be accomplished in previously established photocatalytic systems, such as intermolecular [2+2]cycloadditions of styrenes with electron-deficient olefins.
Heterogeneous catalysts and methods of making and using thereof are described herein.
An “aryl radical” or “aryl group” is understood to mean a radical containing a structure made up of 6 to 30 carbon atoms, 6 to 18 carbon atoms, which is formed from one aromatic ring or a plurality of fused aromatic rings. Exemplary aryl radicals are, without limitation, phenyl, naphthyl, anthracenyl, or phenanthrenyl. Aryl radicals may be unsubstituted, where all carbon atoms which are substitutable bear hydrogen atoms. Alternatively, they may be substituted at one, greater than one, or at all substitutable positions therein. Suitable exemplary substituents include, without limitation, alkyl radicals, such as alkyl radicals having 1 to 8 carbon atoms, which may be selected from methyl, ethyl, i-propyl or t-butyl, aryl radicals (such as C6-aryl radicals, which may be substituted or unsubstituted), heteroaryl radicals (which may comprise at least one nitrogen atom, such as pyridyl radicals), alkenyl radicals (which may comprise one double bond and 1 to 8 carbon atoms), or groups with electron donating or electron accepting ability. Groups with electron donating ability are understood to mean groups which have a positive inductive (+I) and/or positive mesomeric (+M) effect, and groups with electron accepting ability are understood to mean groups which have a negative inductive (−I) and/or negative mesomeric (−M) effect. Suitable groups with donor or acceptor action are halogen radicals, such as F, Cl, Br, alkoxy radicals, aryloxy radicals, carbonyl radicals, ester radicals, amine radicals, amide radicals, CH2F groups, CHF2 groups, CF3 groups, CN groups, thio groups, or SCN groups.
A “heteroaryl radical” or “heteroaryl group” is understood to mean radicals which differ from the aryl radicals described above in that at least one carbon atom in the structure making up the aryl radical is otherwise replaced by at least one heteroatom. Heteroatoms may have hydrogen substituents and/or any permissible substituents of organic compounds in order to satisfy the valences of the heteroatoms. Exemplary heteroatoms include N, O, and S. In most instances, one or two carbon atoms of the structure of the aryl radicals are replaced by heteroatoms. Exemplary heteroaryls include, without limitation, pyridyl, pyrimidyl, pyrazyl, triazyl, and five-membered heteroaromatics, such as pyrrole, furan, thiophene, pyrazole, imidazole, triazole, oxazole, thiazole. Heteroaryls may be substituted at none (unsubstituted), one, more than one, or at all substitutable positions. Suitable substituents are as defined above for the aryl radicals.
An “alkyl radical” or “alkyl group” is understood to mean a radical having 1 to 20 carbon atoms, 1 to 10 carbon atoms, or 1 to 8 carbon atoms. The alkyl radical may be branched or unbranched and the carbon chain may optionally be interrupted by one or more heteroatoms, such as N, O, or S. Heteroatoms may have hydrogen substituents and/or any permissible substituents of organic compounds in order to satisfy the valences of the heteroatoms. The alkyl radical may optionally be substituted by one or more of the substituents mentioned for the aryl radicals above. It is also possible that the alkyl radical contain one or more aryl groups thereon, where suitable aryl groups are described above. Exemplary alkyl radicals include, without limitation, methyl, ethyl, i-propyl, n-propyl, i-butyl, n-butyl, t-butyl, sec-butyl, i-pentyl, n-pentyl, sec-pentyl, neopentyl, n-hexyl, i-hexyl and sec-hexyl.
An “alkenyl radical” or “alkenyl group” is understood to mean a radical having 2 to 20 carbon atoms, 2 to 10 carbon atoms, or 2 to 8 carbon atoms, which may be optionally substituted and at least one carbon-carbon double bond.
An “alkynyl radical” or “alkynyl group” is understood to mean a radical having 2 to 20 carbon atoms, 2 to 10 carbon atoms, or 2 to 8 carbon atoms, which may be optionally substituted and at least one carbon-carbon triple bond.
A “cycloalkyl radical” or “cycloalkyl group” is understood to mean a cyclic radical having 3 to 20 carbon atoms, 3 to 10 carbon atoms, or 3 to 8 carbon atoms. The carbon chain of the cycloalkyl radical may optionally be interrupted by one or more heteroatoms, such as N, O, or S forming a heterocycloalkyl. Heteroatoms may have hydrogen substituents and/or any permissible substituents of organic compounds in order to satisfy the valences of the heteroatoms. The cycloalkyl radical may be unsubstituted or substituted, i.e. substituted by one or more of the substituents mentioned herein.
A “cycloalkenyl radical” or “alkenyl group” is understood to mean a cyclic radical having 4 to 20 carbon atoms, 4 to 10 carbon atoms, or 4 to 8 carbon atoms, which may be optionally substituted and at least one carbon-carbon double bond.
A “cycloalkynyl radical” or “cycloalkynyl group” is understood to mean a cyclic radical having 6 to 20 carbon atoms, 6 to 10 carbon atoms, or 6 to 8 carbon atoms, which may be optionally substituted and at least one carbon-carbon triple bond.
“Carbonyl group,” as used herein, is understood to mean moieties which can be represented by the general formula:
wherein X is a bond, or represents an oxygen or a sulfur, and R represents a hydrogen, a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, —(CH2)m—R″; wherein R′ represents a hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl or —(CH2)m—R″; wherein R″ represents a hydroxy group, substituted or unsubstituted carbonyl group, an aryl, a cycloalkyl, a heterocycle, or a polycycle; and m is zero or an integer ranging from 1 to 8. Where X is oxygen and R is defined as above, the moiety can be referred to as a “carboxyl group.” When X is oxygen and R is hydrogen, the formula represents a “carboxylic acid group.” Where X is oxygen and R′ is hydrogen, the formula represents a “formate group.” Where X is oxygen and R or R′ is not hydrogen, the formula represents an “ester group.” In general, where the oxygen atom of the above formula is replaced by a sulfur atom, the formula represents a “thiocarbonyl group.” Where X is sulfur and R or R′ is not hydrogen, the formula represents a “thioester group.” Where X is sulfur and R is hydrogen, the formula represents a “thiocarboxylic acid group.” Where X is sulfur and R′ is hydrogen, the formula represents a “thioformate group.” Where X is a bond and R is not hydrogen, the above formula represents a “ketone group.” Where X is a bond and R is hydrogen, the above formula represents an “aldehyde group.” The term “substituted carbonyl” refers to a carbonyl, as defined above, wherein one or more hydrogen atoms in R, R′ or a group to which the moiety is attached, are independently substituted with suitable substituents, as defined below.
An “amide group” or “amido” is understood to mean a moiety represented by the general formula:
wherein, E is absent, or E is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, wherein independently of E, R and R′ each independently represent a hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbonyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, —(CH2)m—R″′, or R and R′ taken together with the N atom to which they are attached complete a heterocycle having from 3 to 14 atoms in the ring structure; R′″ can represent a hydroxy group, substituted or unsubstituted carbonyl group, an aryl group, a cycloalkyl group, a heterocycle, or a polycycle; and m is zero or an integer ranging from 1 to 8. When E is oxygen, a “carbamate group” is formed. The carbamate cannot be attached to another chemical species, such as to form an oxygen-oxygen bond, or other unstable bonds, as understood by one of ordinary skill in the art.
The term “substituted,” as used herein, refers to all permissible substituents of the compounds or functional groups described above. Exemplary substituents include, but are not limited to, halogens, hydroxyl groups, or any other organic groupings containing any number of carbon atoms, preferably 1-14 carbon atoms, and optionally include one or more heteroatoms, such as oxygen, sulfur, or nitrogen grouping in linear, branched, or cyclic structural formats. Representative substituents can include alkyl, substituted alkyl (such as —CF3 and —CD3), alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halo, hydroxyl, alkoxy, formyl, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, thio (—SH), substituted thio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, carboxylates, amino, substituted amino, amide, substituted amide, sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, substituted phosphonyl, polyaryl, substituted polyaryl, cyclic (such as C3-C20 cyclic), substituted cyclic (such as substituted C3-C20 cyclic), heterocyclic, substituted heterocyclic, deuterium, trihaloalkyl (trifluoromethyl), unsubstituted diarylamino, substituted diarylamino, unsubstituted dialkylamino, substituted dialkylamino, azo, carbonate ester, nitro, nitroso, phosphino, pyridyl, NRR′, SR, C(O)R, COOR, C(O)NR, SOR, and SOR groups, wherein R and R′ are independently selected from hydrogen atom, deuterium atom, or any of the substituents named above.
Numerical ranges disclosed in the present application include, but are not limited to, ranges of carbon atoms, ranges of temperatures, ranges of concentrations, ranges of times, amongst other ranges disclosed below. The disclosed ranges, disclose individually each possible number that such a range could reasonably encompass, as well as any sub-ranges and combinations of sub-ranges encompassed therein. For example, disclosure of a range of carbon atoms is intended to disclose individually every possible value that such a range could encompass, consistent with the disclosure herein. For example, a carbon range of 1 to 10 carbons also discloses each number of carbons within the range individually (1, 2, 3, 4, 5, 6, 7, 8, 9, 10 carbons), as well as any sub-range contained therein (2 to 4 carbons or 5 to 9 carbons).
“Electron withdrawing group,” as used herein refers to a functional group or
atom within a molecule that has a tendency to withdraw electron density from the rest of the molecule typically due to its electronegative nature or its ability to attract electrons through resonance or inductive effects. Electron withdrawal can occur through different mechanisms, such as: (1) Electronegativity; (2) Resonance Effects; (3) Inductive Effects. Non-limiting exemplary functional groups include carbonyl groups (C═O), nitro groups (—NO2), and halogens (e.g., —Cl, —Br, —I).
Use of the term “about” is intended to describe values either above or below the stated value, which the term “about” modifies, in a range of approx. +/−10%; in other instances the values may range in value either above or below the stated value in a range of approx. +/−5%. When the term “about” is used before a range of numbers (i.e., about 1-5) or before a series of numbers (i.e., about 1, 2, 3, 4, etc.) it is intended to modify both ends of the range of numbers and/or each of the numbers recited in the entire series, unless specified otherwise.
Heterogeneous catalysts which can be used in chemical reactions, such as [2+2]cycloadditions are described herein. In one instance, a non-limiting example a heterogenous catalyst includes:
In some instances, the phosphine ligand can have a chemical structure according to the genus formula below:
In some instances, the plurality of inorganic nodes of the heterogenous catalyst include or are [Zr6] inorganic nodes. In some instances, the plurality of organic linkers of the heterogenous catalyst include quaterphenyl dicarboxylate organic linkers. In certain instances, the quaterphenyl dicarboxylate organic linkers include or are tetramethyl substituted quaterphenyl dicarboxylate organic linkers. In certain instances, the tetramethyl substituted quaterphenyl can be 2′,2″,5′,5″-tetramethyl-[1,1′:4′,1″:4″,1″′-quaterphenyl]-4,4″′-dicarboxylic acid.
The heterogenous catalyst includes at least one organic linker which has a phenanthroline moiety, which can be derived from 4,4′-(1,10-phenanthroline-3,8-diyl)dibenzoic acid. “Derived,” as used herein refers to the molecule which was used to synthesize the metal-organic framework (MOF) and is understood to become part of the MOF structure.
In preferred instances, the metal-organic framework is a Universitetet Oslo-69 metal-organic framework. In preferred instances, the metal-organic framework is microporous. In some instances, the metal-organic framework has a Brunauer-Emmett-Teller (BET) surface area of at least about 1,000 m2 g−1, 1,250 m2 g−1, 1,500 m2 g−1, 1,750 m2 g−1, or 2,000 m2 g−1; or the metal-organic framework has a Brunauer-Emmett-Teller (BET) surface area in a range from between about 1,000 and 2,000 m2 g−1, as well as sub-ranges or individual values contained within the aforementioned range. In some instances, the metal-organic framework has pore width distribution centered at about 1.3, 1.4, 1.5, 1.6, or 1.7 nm; or the metal-organic framework has pore width distribution centered in a range from between about 1.2 to 1.8 nm, as well as sub-ranges or individual values contained within the aforementioned range.
In certain instances, the catalyst complex within the metal-organic framework includes a chemical structure as follows:
where the wavy bonds extending from the phenanthroline moiety are understood by the skilled artisan to be part of an organic linker containing the moiety within the metal-organic framework.
The heterogeneous catalysts (i.e., heteroleptic copper(I) complexes with bidentate nitrogen and phosphorus donor ligands) function as photoredox catalysts and (high) triplet photosensitizers, which can be used for a wide range of light-mediated organic transformations. It is believed that anchoring the catalyst complex within the MOF framework improves the photostability of such copper-binap complexes. Heterogenizing the labile transition metal species onto such suitable framework matrices can provide for catalyst-site isolation(Rogge, S. M. et al. Metal-organic and covalent organic frameworks as single-site catalysts. Chem. Soc. Rev. 46, 3134-3184 (2017); Wei, Y.-S., Zhang, M., Zou, R. & Xu, Q. Metal-organic framework-based catalysts with single metal sites. Chem. Rev. 120, 12089-12174 (2020); Chen, W. et al. Site-isolated azobenzene-containing metal-organic framework for cyclopalladated catalyzed Suzuki-Miyuara coupling in flow. ACS Appl. Mater. Interfaces 13, 51849-51854 (2021)). For example, by incorporating binap-ligated heteroleptic copper(I) species onto the organic linker of a structurally stable MOF support it was found that it was possible to prevent the photoinduced decomposition of copper triplet photosensitizers and extend their excited-state lifetimes due to MOF-enabled confinement effects(Liu, J. et al. MOF-enabled confinement and related effects for chemical catalyst presentation and utilization. Chem. Soc. Rev. 51, 1045-1097 (2022)) (see
The heterogeneous catalysts can provide high turnover numbers (TON) in a range of about 50 to 5000 turnovers, as well as sub-ranges or individual values contained within the aforementioned range.
The heterogeneous catalysts typically have relatively long photoexcited-state lifetimes. For instance, the heterogeneous catalysts can have an excited-state lifetime at room temperature of at least about 3, 3.5, 4, 4.5, or 5 μs; or an excited-state lifetime at room temperature in a range of between about 3 to 5 μs, as well as sub-ranges or individual values contained within the aforementioned range.
The heterogeneous catalysts described can be synthesized by various methods. In one instance, a non-limiting method of synthesizing a heterogenous catalyst includes the steps of:
In another non-limiting instance, a method of synthesizing a heterogenous catalyst includes the steps of:
In some instances, the phosphine ligand can have a chemical structure according to:
In certain instances, the inorganic salt used in step (i) of the first method is a zirconium salt, such as ZrCl4. Other inorganic salts are known to the person of ordinary skill in the art. In some instances, the plurality of inorganic nodes of the metal-organic framework include or are [Zr6] inorganic nodes.
In some instances of the methods, the plurality of organic linkers of the heterogenous catalyst formed include quaterphenyl dicarboxylate organic linkers. In certain instances, the quaterphenyl dicarboxylate organic linkers include or are tetramethyl substituted quaterphenyl dicarboxylate organic linkers. In certain instances, the tetramethyl substituted quaterphenyl can be 2′,2″,5′,5″-tetramethyl-[1,1′:4′,1″:4″,1″′-quaterphenyl]-4,4″′-dicarboxylic acid.
The heterogenous catalyst formed according to the methods above includes at least one organic linker which has a phenanthroline moiety, which can be derived from 4,4′-(1,10-phenanthroline-3,8-diyl)dibenzoic acid. “Derived,” as used herein refers to the molecule which was used to synthesize the metal-organic framework (MOF) and is understood to become part of the MOF structure.
In preferred instances, the metal-organic framework is a Universitetet Oslo-69 metal-organic framework. In preferred instances, the metal-organic framework is microporous.
In certain instances of the first method, step (i) proceeds in an organic solvent comprising a Lewis acid and heating at a temperature of at least about 100° C.; wherein the organic solvent is optionally dimethylformamide and the Lewis acid is optionally trifluoroacetic acid.
Typically, the metalating step of the methods proceeds in an organic solvent at room temperature under an inert atmosphere; optionally where the organic solvent is dichloromethane and optionally wherein the inert atmosphere is a nitrogen atmosphere.
In certain instances of the methods, the metal complex used in the metaling step is:
Other metal complexes may be used to achieve the described heterogeneous catalysts.
In preferred instances, the methods produce a heterogeneous catalyst where the catalyst complex attached to the metal-organic framework has a chemical structure as follows:
where the wavy bonds extending from the phenanthroline moiety are understood by the skilled artisan to be part of an organic linker containing the moiety within the metal-organic framework.
The skilled person understands that the heterogeneous catalysts described above and synthesized by the exemplary methods may have one or more chiral centers and thus exist as one or more stereoisomers. Such stereoisomers can exist as a single enantiomer, a mixture of diastereomers or a racemic mixture are encompassed by the present disclosure. As used herein, the term “stereoisomers” refers to compounds made up of the same atoms having the same bond order but having different three-dimensional arrangements of atoms which are not interchangeable. The three-dimensional structures are called configurations. As used herein, the term “enantiomers” refers to two stereoisomers which are non-superimposable mirror images of one another. As used herein, the term “optical isomer” is equivalent to the term “enantiomer”. As used herein the term “diastereomer” refers to two stereoisomers which are not mirror images but also not superimposable. The terms “racemate”, “racemic mixture” or “racemic modification” refer to a mixture of equal parts of enantiomers. The term “chiral center” refers to a carbon atom to which four different groups are attached. Choice of the appropriate chiral column, eluent, and conditions necessary to effect separation of the pair of enantiomers is well known to one of ordinary skill in the art using standard techniques (see e.g. Jacques, J. et al., “Enantiomers, Racemates, and Resolutions”, John Wiley and Sons, Inc. 1981).
For the methods described, the synthetic conditions (choice of solvent(s), temperatures, atmospheres, work-up conditions, purification conditions, etc.) can be selected or modified, as appropriate, by the person of ordinary skill in the art of synthetic chemistry.
The formed heterogeneous catalysts may be characterized using suitable techniques known to the person of ordinary skill. Without limitation, the heterogeneous catalysts synthesized according to the methods described can be analyzed via 1H and 13C NMR, ICP-AES, BET analysis, powder XRD, EDS, XPS, EXAFS, TGA, and combinations thereof.
The heterogeneous catalysts described can be used in large-scale synthesis and demonstrate catalyst recyclability, as well as facilitate the separation of catalyst and product. Moreover, the heterogeneous catalysts can be employed to achieve organic transformations that are not known to be accomplished in previously established photocatalytic systems, such as intermolecular [2+2]cycloadditions of styrenes with electron-deficient olefins.
At present, the cost for producing the heterogeneous copper photocatalysts is about 30 to 50 times lower than the cost of producing commercialized noble-metal photocatalysts. In general, homogeneous noble-metal photocatalysts cannot be recycled after a photocatalytic reaction, whereas the heterogeneous catalysts described can be recovered from the reaction mixture without significant loss of reactivity. This is in contrast to the tedious separation processes used to remove homogeneous photocatalysts from solution, separation in heterogeneous photocatalysis can be achieved through filtration methods known to the skilled person.
In one non-limiting instance, the heterogeneous catalysts can be used to perform a [2+2]cycloaddition, in a method including the steps of:
As discussed in the examples, a cyclobutane is formed from the [2+2]cycloaddition between the carbon-carbon double bonds of the first and the second compounds.
In some instances of the method, at least one of the first and the second compounds is or includes an electron deficient alkene therein. In other instances, at least one of the first and the second compounds is a styrene compound or a vinylnapthalene compound, which may be substituted. In still other instances, at least one of the first and/or the second compounds comprises an U,D-unsaturated carbonyl. In certain instances, at least one of the first and/or the second compounds has a chemical structure as follows:
wherein EWG is an electron withdrawing group. Without limitation, the electron withdrawing group can be selected from —C(O)OR; —C(O)R′; —C(O)NR1R2, or —CN; where R, R′, R1, and R2 are each independently selected from hydrogen; halogen group (i.e., —F, —Cl, —Br, —I); a C1-C5 alkyl group (linear or branched), such as a methyl, ethyl, propyl, butyl, or pentyl group; alkenyl group; alkynyl group; cycloalkyl group; cycloalkenyl group; cycloalkynyl group; a hydroxyl group; an aryl group (i.e., a phenyl group); a heteroaryl group; a benzyl group; an acyl group; an ester group; a carbonyl group; a carboxylate group; an amino group (primary, secondary, or tertiary); an amide group; and a nitro group. In other instances, at least one of the first and/or the second compounds can have a chemical structure according to any one of Formulae (I)-(IV):
Various combinations of first and the second compounds including carbon-carbon double bonds capable of undergoing a [2+2]cycloaddition, as named above, are possible.
In some instances of the method, the heterogenous catalyst can be present in the mixture in a concentration of between about 0.01 to 2 mol % of the total mixture.
In some cases, the mixture further includes 4-dimethylaminopyridine.
In some instances, wherein the visible light irradiation includes blue light, where the blue light can be at or include a wavelength of 440 nm.
In some instances, the organic solvent is or includes 1,2-dichloroethane. Other suitable organic solvents may be used.
Step (b) typically proceeds under an inert atmosphere, where the inert atmosphere can be a nitrogen atmosphere. Other suitable inert atmospheres can be used (i.e., argon, etc.).
For the method described, a further step of recovering the heterogeneous catalyst from the mixture following step (b) can be carried out. As mentioned above, such recovery can be accomplished using art known filtration techniques. The recovered heterogeneous catalyst can be reused to perform another [2+2]cycloaddition at least one, two, three, four, five, six, or more times without loss of reactivity or significant loss of reactivity. “Significant loss,” as used herein, refers to a loss of reactivity of no more than about 10, 20, 30, 40, or 50% of the reactivity, as compared to the catalyst when first used.
The heterogeneous catalysts can provide high turnover numbers (TON) in catalyzing cycloaddition products, where the TON can be in a range of about 50 to 5000 turnovers, as well as sub-ranges or individual values contained within the aforementioned range.
The skilled person understands that the [2+2]cycloaddition products described above and synthesized using the heterogeneous catalysts may have one or more chiral centers and thus exist as one or more stereoisomers. Such stereoisomers can exist as a single enantiomer, a mixture of diastereomers or a racemic mixture are encompassed by the present disclosure. As used herein, the term “stereoisomers” refers to compounds made up of the same atoms having the same bond order but having different three-dimensional arrangements of atoms which are not interchangeable. The three-dimensional structures are called configurations. As used herein, the term “enantiomers” refers to two stereoisomers which are non-superimposable mirror images of one another. As used herein, the term “optical isomer” is equivalent to the term “enantiomer”. As used herein the term “diastereomer” refers to two stereoisomers which are not mirror images but also not superimposable. The terms “racemate”, “racemic mixture” or “racemic modification” refer to a mixture of equal parts of enantiomers. The term “chiral center” refers to a carbon atom to which four different groups are attached. Choice of the appropriate chiral column, eluent, and conditions necessary to effect separation of the pair of enantiomers is well known to one of ordinary skill in the art using standard techniques (see e.g. Jacques, J. et al., “Enantiomers, Racemates, and Resolutions”, John Wiley and Sons, Inc. 1981).
For the methods described above, the synthetic conditions (choice of solvent(s), temperatures, atmospheres, work-up conditions, purification conditions, etc.) can be selected or modified, as appropriate, by the person of ordinary skill in the art of synthetic chemistry.
In some instances, the use of the heterogeneous catalysts can provide [2+2]cycloaddition products with high diastereoselectivity. In some instances, the diastereoselectivity is defined as a diastereomeric ration (d.r.), which can be in a range from >1:1 to about 10:1 between to diastereomer products produced, as well as sub-ranges or individual values contained within the aforementioned range.
The heterogeneous catalysts and methods described herein are further illustrated in the following examples, which are provided by way of illustration and are not intended to be limiting. It will be appreciated that variations in proportions and alternatives in elements of the components shown will be apparent to those skilled in the art and are within the scope of disclosed forms. Theoretical aspects are presented with the understanding that Applicant does not seek to be bound by the theory presented.
PXRD patterns were recorded on a Rigaku Ultima IV X-ray diffractometer (CuKα, λ=1.54184 Å), operating at 40 kV and 30 mA. The measurement parameters included a scan speed of 100 min−1, a step size of 0.05° and a scan range of 2θ from 5° to 40°.
Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) mapping were collected on an on VEGA3 TESCAN (Japan). The X-ray photoelectron spectroscopy (XPS) surface investigation was carried out on a Thermo ESCALAB 250Xi system and the spectra were analyzed using the Thermo Scientific Avantage Data System software. Transmission electron microscopy (TEM) and energy dispersive X-ray (EDX) analyses were performed by FEI-Talos F200S.
Inductively couple plasma—atomic emission spectroscopy (ICP-AES) measurements were conducted on a Thermo Scientific iCAP 7000 ICP-AES analyzer.
Thermogravimetric analyses (TGA) was performed on a Mettler-Toledo (TGA/DSC1) thermal analyzer (Q50 V20.6). Approximately 5 mg of dried samples were measured under a N2 flow rate of 20 ml min−1 with a heating rate of 10° C. min−1 from 40 to 800° C.
X-ray diffraction data of single crystals were collected at 173 K on a XtaLab PRO MM007HF DW diffractometer system equipped with a MicroMax-007DW MicroFocus X-ray generator and a Pilatus 200 K silicon diarray detector (Rigaku, Japan, CuKα, λ=1.54184 Å). Structures were solved by direct methods using the SHELXT program and refined by full-matrix least-squares on F2 with anisotropic displacement parameters for all non-hydrogen atoms using the SHELXL program.
X-ray absorption fine structure (XAFS) measurements were performed on beamline 01B1 and 14B2 at SPring-8 of the Japan Synchrotron Radiation Research Institute (8 GeV, 99.5 mA). Spectra of Cu K-edge XAFS (20 min per spectrum) were recorded in a fluorescence mode using an ionization chamber with Si(111) under atmospheric conditions and detuned to reduce the contribution of higher-order harmonics below the level of noise. A metallic foil standard was used as a reference for energy calibration and was measured simultaneously with the experimental samples. Ion chambers filled with N2 (100%) and N2 (70%)/Ar (30%) were used for the I0 and If detectors. XAFS results were processed according to the standard procedures using the ATHENA module in the IFEFFIT software packages. The k3-weighted EXAFS spectra were obtained by subtracting the post-edge background from the overall absorption and then normalising with respect to the edge-jump step. Subsequently, k3-weighted x(k) data of Cu K-edge were Fourier transformed to R-space using Hanning windows (dk=1.0 Å−1) to separate the EXAFS contributions from different coordination shells. To obtain the quantitative structural parameters around central atoms, least-squares curve parameter fitting was performed using the ARTEMIS module in the IFEFFIT software packages. Refinement was performed by optimizing an amplitude factor S02 and energy shift ΔE0 which are common to all paths, in addition to parameters for bond length (ΔR) and Debye-Waller factor (σ2). The fitting models for the Cu sites in UiO-69-phen(binap)Cu and UiO-69-phen(xantphos)Cu were based on the crystal structures of Cu-1 (CCDC: 2240330) and Cu-3 (CCDC: 2244329), respectively.
Solid-state UV-Vis absorption spectra of the framework materials were recorded at room temperature on a UV-2550 spectrophotometer (SHIMADZU, Japan).The steady-state emission spectra were measured on a Horiba Fluorog-3 spectrophotometer. The lifetime measurements were performed on a Quanta Ray GCR 150-10 PULSED Nd:YAG laser system.
Brunauer-Emmett-Teller (BET) surface area analysis was performed on a micromeritics surface area analyzer (ASAP 2420) at 77 K.
Cyclic voltammograms were performed on a CHI760E electrochemistry workstation. Regular 3-electrode systems were used. Measurements were recorded in a DMF solution of (Bu4N)(ClO4) (0.1 M) at a scan rate of 100 mV s−1 under the protection of N2 using a glassy carbon disk (d=0.3 cm) as a working electrode and a platinum plate (1 cm×1 cm) as a counter electrode. An Ag/AgCl (3 M KCl) electrode was used as a reference electrode in all the experiments, and its potential (−0.53 V vs. Fc/Fc) was calibrated with the ferrocenium/ferrocene (Fc+/Fc) redox couple.
1H and 13C NMR spectra were recorded on a Bruker 500 or Bruker 400 spectrometer in CDCl3, DMSO-d6 or a mixed deuterated solvent.
High-resolution electron ionization (EI) mass spectra were recorded on a Thermo Scientific DFS Magnetic Sector GC-HRMS system. High-resolution electrospray ionization mass spectrometry (ESI-MS) measurements were performed on a Bruker impact II high-resolution LC-QTOF mass spectrometer. Accurate masses from high-resolution mass spectra were reported for the molecular ion [M]+ or [M+H]+.
ZrCl4 (179 mg, 0.77 mmol), 4,4′-(1,10-phenanthroline-3,8-diyl)dibenzoic acid (L2) (50 mg, 0.12 mmol), 2′,2″,5′,5″-tetramethyl-[1,1′:4′,1″:4″,1′″-quaterphenyl]-4,4″′-dicarboxylic acid (L3) (270 mg, 0.60 mmol), and trifluoroacetic acid (0.4 ml) were ultrasonically dispersed in N,N-dimethylformamide (DMF) (34 ml). The resulting solution was heated to 100° C. in a 50-ml glass tube for 72 hours. After cooling to room temperature, the supernatant was decanted and the solid was washed five times with DMF and acetone. UiO-69-phen was then collected by filtration and dried in air to give a white solid (389 mg, 60% yield based on linkers). The product (2 mg) was digested in a mixture of a saturated K3PO4/D2O solution and DMSO-d6 (0.6 ml, 1:2 v/v) and subjected to 1H NMR analysis. The ratio of L2 and L3 was found to be 1:5. The chemical formula of UiO-69-phen was determined to be Zr6O4(OH)4(L2)(L3)5·4.0DMF based on NMR digestion data and TGA.
UiO-69-phen (30.0 mg, 5.6 μmol based on L2) was immersed in a 2-ml dichloromethane solution of [Cu(MeCN)4](PF6) (10.4 mg, 28 μmol) and stirred under N2 atmosphere at 60° C. for 4 hours. After cooling to room temperature, the supernatant was decanted and the solid was washed five times with DMF and acetone. UiO-69-phenCu was then collected by filtration and dried in air to give a green solid (22.7 mg, 93% yield). ICP-AES analysis indicated a Zr/Cu ratio of 6:1. The chemical formula of UiO-69-phenCu was determined to be {Zr6O4(OH)4(L2)(L3)5[Cu(CH3CN)2PF6]}·4.4DMF based on ICP-AES and TGA.
UiO-69-phen (30.0 mg, 5.6 μmol based on L2) was immersed in a 2-ml dichloromethane solution of [Cu(xantphos)(MeCN)2](PF6) (24.3 mg, 28 μmol) and stirred under N2 atmosphere at room temperature for 9 hours. After post-synthetic metalation, the supernatant was decanted and the solid was washed five times with DMF and acetone. UiO-69-phen(xantphos)Cu was then collected by filtration and dried in air to give a yellow solid (30.9 mg, 91% yield). ICP-AES analysis indicated a Zr/Cu ratio of 6:1. The product (2 mg) was digested in a solution of D3PO4/D2O/DMSO-d6 (1:1:5 v/v/v) and subjected to 1H NMR analysis. The ratio of Cu-4 and L3 was found to be 1:5. The chemical formula of UiO-69-phen(xantphos)Cu was determined to be {Zr6O4(OH)4(L2)(L3)5[Cu(xantphos)PF6]}·4.9DMF based on NMR digestion data and TGA.
UiO-69-phen (300 mg, 56 μmol based on L2) was immersed in a 20-ml dichloromethane solution of [Cu(binap)(MeCN)2](PF6) (256 mg, 0.28 mmol) and stirred under N2 atmosphere at room temperature for 9 hours. After post-synthetic metalation, the supernatant was decanted and the solid was washed five times with DMF and acetone. UiO-69-phen(binap)Cu was then collected by filtration and dried in air to give a yellow solid (312 mg, 94% yield). ICP-AES analysis indicated a Zr/Cu ratio of 6:1. The product (2 mg) was digested in a solution of D3PO4/D2O/DMSO-d6 (1:1:5 v/v/v) and subjected to 1H NMR analysis. The ratio of Cu-2 and L3 was found to be 1:5. The chemical formula of UiO-69-phen(binap)Cu was determined to be {Zr6O4(OH)4(L2)(L3)5[Cu(binap)PF6]}·6.0DMF based on NMR digestion data and TGA.
General Procedure for the Photoinduced Crossed [2+2] Cycloaddition of Styrenes with Electron-Deficient Alkenes:
To a 25-ml flame-dried Schlenk tube cooled under N2 atmosphere were added UiO-69-phen(binap)Cu (2.4 mg, 0.4 μmol based on Cu, 0.2 mol %), 4-dimethylaminopyridine (29 mg, 0.24 mmol, 1.2 equiv.), 1,2-dichloroethane (1.0 ml), styrene (0.2 mmol, 1.0 equiv.), and electron-deficient alkene (0.6 or 1.0 mmol, 3.0 or 5.0 equiv.) sequentially. After three freeze-pump-thaw cycles, the reaction mixture was irradiated by three 40-watt Kessil PR160L-440 blue-LED lamps at room temperature (with three fans) for 48 hours. After irradiation, ethyl acetate (10 ml) was added into the crude mixture; the resulting solution was filtered through a pad of silica gel and washed four times with ethyl acetate (4×10 ml). The combined filtrates were concentrated under vacuum and the diastereomeric ratio was determined by 1H NMR analysis. The residue was purified by flash column chromatography on silica gel to afford the corresponding product.
To a 25-ml flame-dried Schlenk tube cooled under N2 atmosphere were added UiO-69-phen(binap)Cu (2.4 mg, 0.4 μmol based on Cu, 0.02 mol %), 4-dimethylaminopyridine (293 mg, 2.4 mmol, 1.2 equiv.), 1,2-dichloroethane (1.0 ml), styrene (2.0 mmol, 1.0 equiv.), and the other coupling styrene (10 mmol, 5.0 equiv.) sequentially. After three freeze-pump-thaw cycles, the reaction mixture was irradiated by three 40-watt Kessil PR160L-440 blue-LED lamps at room temperature (with three fans) for 48 hours. After irradiation, ethyl acetate (10 ml) was added into the crude mixture; the resulting solution was filtered through a pad of silica gel and washed four times with ethyl acetate (4×10 ml). The combined filtrates were concentrated under vacuum and the diastereomeric ratio was determined by 1H NMR analysis. The residue was purified by flash column chromatography on silica gel to afford the corresponding product.
General Procedure for the Photoinduced Crossed [2+2] Cycloaddition of Exocyclic Arylidene Azetidines, Thietanes, and Oxetanes with Electron-Deficient Alkenes and Styrenes:
To a 25-ml flame-dried Schlenk tube cooled under N2 atmosphere were added UiO-69-phen(binap)Cu (2.4 mg, 0.4 μmol based on Cu, 0.2 mol %), 4-dimethylaminopyridine (29 mg, 0.24 mmol, 1.2 equiv.), 1,2-dichloroethane (1.0 ml), exocyclic arylidene azetidine, thietane, or oxetane (0.2 mmol, 1.0 equiv.), and electron-deficient alkene or styrene (0.6 mmol, 3.0 equiv.) sequentially. After three freeze-pump-thaw cycles, the reaction mixture was irradiated by three 40-watt Kessil PR160L-440 blue-LED lamps at room temperature (with three fans) for 48 hours. After irradiation, ethyl acetate (10 ml) was added into the crude mixture; the resulting solution was filtered through a pad of silica gel and washed four times with ethyl acetate (4×10 ml). The combined filtrates were concentrated under vacuum and the diastereomeric ratio was determined by 1H NMR analysis. The residue was purified by flash column chromatography on silica gel to afford the corresponding product.
To a 100-ml flame-dried Schlenk tube cooled under N2 atmosphere were added UiO-69-phen(binap)Cu (89 mg, 15 μmol based on Cu, 0.15 mol %), 4-dimethylaminopyridine (1.46 g, 12 mmol, 1.2 equiv.), 1,2-dichloroethane (50 ml), 1-vinylnaphthalene (1.54 g, 10 mmol, 1.0 equiv.), methyl acrylate (4.5 ml, 50 mmol, 5.0 equiv.) sequentially. After three freeze-pump-thaw cycles, the reaction mixture was irradiated by three 40-watt Kessil PR160L-440 blue-LED lamps at room temperature (with three fans) for 48 hours. After irradiation, ethyl acetate (100 ml) was added into the crude mixture; the resulting solution was filtered through a pad of silica gel and washed four times with ethyl acetate (4×50 ml). The combined filtrates were concentrated under vacuum and the diastereomeric ratio was determined by 1H NMR analysis. The residue was purified by flash column chromatography on silica gel to afford 1 (1.68 g, 70% yield) as a colorless oil.
To accommodate a sterically hindered heteroleptic copper-binap complex in crystalline porous frameworks (Zhou, H.-C., Long, J. R. & Yaghi, O. M. Introduction to metal-organic frameworks. Chem. Rev. 112, 673-674 (2012); Furukawa, H., Cordova, K. E., O'Keeffe, M. & Yaghi, O. M. The chemistry and applications of metal-organic frameworks. Science 341, 1230444 (2013)), the highly stable Universitetet i Oslo-69 (UiO-69) MOF (Cavka, J. H. et al. A new zirconium inorganic building brick forming metal organic frameworks with exceptional stability. J. Am. Chem. Soc. 130, 13850-13851 (2008); Newsome, W. J. et al. Solid state multicolor emission in substitutional solid solutions of metal-organic frameworks. J. Am. Chem. Soc. 141, 11298-11303 (2019)), which consists of [Zr6] inorganic nodes and quaterphenyl dicarboxylate organic linkers, was chosen as a photocatalyst support. Considering that binap-ligated copper(I) complexes are intolerant of the solvothermal conditions for the MOF synthesis, a post-synthetic metalation method (Kalaj, M. & Cohen, S. M. Postsynthetic modification: an enabling technology for the advancement of metal-organic frameworks. ACS Cent. Sci. 6, 1046-1057 (2020); Li, J. et al. Self-adaptive dual-metal-site pairs in metal-organic frameworks for selective CO2 photoreduction to CH4. Nat. Catal. 4, 719-729 (2021); Ma, X. et al. Modulating coordination environment of single-atom catalysts and their proximity to photosensitive units for boosting MOF photocatalysis. J. Am. Chem. Soc. 143, 12220-12229 (2021)) was utilized rather than pre-synthetic modification of MOF linkers (Wang, C., Xie, Z., deKrafft, K. E. & Lin, W. Doping metal-organic frameworks for water oxidation, carbon dioxide reduction, and organic photocatalysis. J. Am. Chem. Soc. 133, 13445-13454 (2011); Wang, C., deKrafft, K. E. & Lin, W. Pt nanoparticles@photoactive metal-organic frameworks: efficient hydrogen evolution via synergistic photoexcitation and electron injection. J. Am. Chem. Soc. 134, 7211-7214 (2012)) to introduce the targeted copper species onto the UiO-69 MOF (
Immersing UiO-69-phen in a dichloromethane solution of [Cu(xantphos)(MeCN)2](PF6) or [Cu(binap)(MeCN)2](PF6) at room temperature produced MOF-supported heteroleptic copper photocatalyst UiO-69-phen(xantphos)Cu or UiO-69-phen(binap)Cu. When the same metalation conditions were applied to non-functionalized UiO-69 MOF without a phen-containing linker, no heterogeneous copper catalyst was produced. It is worth noting that the phen-functionalized UiO-67 MOF with a much smaller pore width distribution (Zhang, X. et al. Catalytic chemoselective functionalization of methane in a metal-organic framework. Nat. Catal. 1, 356-362 (2018)) was unable to accommodate the bulky cationic binap-ligated copper(I) complex even at elevated temperatures. Additionally, attempts to directly encapsulate the desired copper(I) species in conventional porous hosts, such as UiO-67 and UiO-68 MOFs, did not produce the corresponding heterogeneous binap-containing copper photosensitizers, presumably due to the low thermal stability of binap-ligated copper(I) complexes upon heating and their poor compatibility with strong Lewis acids. The heterogenized copper(I) species (UiO-69-phenCu) without chelation of bisphosphine ligands was prepared by treating UiO-69-phen with [Cu(MeCN)4](PF6) at 60° C. According to the inductively coupled plasma atomic emission spectroscopy (ICP-AES) and nuclear magnetic resonance (NMR) analysis, approximately one copper atom per [Zr6] node was successfully loaded onto the MOF support in all three cases. The consistency of copper contents determined by ICP-AES and NMR analysis, along with the absence of other phosphine-containing species in the NMR digestion samples, ruled out the possibility of bisphosphine-chelated copper(I) complexes occluding the MOF pores during post-synthetic metalation. The N2 adsorption isotherms for these copper-loaded MOFs suggested that the microporosity was preserved despite the decrease in the BET surface area. A typical octahedral morphology of UiO-69 MOFs was maintained upon post-synthetic metalation (SEM image not shown). The powder X-ray diffraction (PXRD) patterns revealed that the MOF crystallinity remained unchanged after the metalation processes (
The copper coordination environments in the pores of UiO-69-phen(binap)Cu and UiO-69-phen(xantphos)Cu were further investigated using X-ray absorption spectroscopy at the Cu K-edge (
It was hypothesized that 1-vinylnaphthalene, having a relatively low triplet energy, would engage in energy transfer with photoexcited copper catalysts and then undergo an unprecedented [2+2]cycloaddition with methyl acrylate (Murray, P. R. D. et al. Intermolecular crossed [2+2]cycloaddition promoted by visible-light triplet photosensitization: expedient access to polysubstituted 2-oxaspiro[3.3]heptanes. J. Am. Chem. Soc. 143, 4055-4063 (2021); Coote, S. C. & Bach, T. Enantioselective intermolecular [2+2] photocycloadditions of isoquinolone mediated by a chiral hydrogen-bonding template. J. Am. Chem. Soc. 135, 14948-14951 (2013)) to afford trans-methyl 2-(naphthalen-1-yl)cyclobutane-1-carboxylate (1), as shown in Scheme 1 below.
After a systematic study of various reaction parameters, a procedure was established that achieved the cycloaddition product using 0.2 mol % of UiO-69-phen(binap)Cu, with a turnover number (TON) of 365 and a diastereoselectivity of >10:1 (see Table 1, entry 1 below). Control experiments demonstrated that the reaction did not take place in the absence of light or photocatalysts. Other MOF-supported copper(I) complexes lacking binap coordination failed to provide any cycloaddition products (Table 1, entries 2 and 3), which indicates the formation of binap-based copper(I) photosensitizers is important for promoting the crossed [2+2]cycloaddition. The low reactivity of the homogeneous counterparts (Cu-1 and Cu-2) highlighted the significance of immobilizing the heteroleptic copper(I) complex on the MOF support in order to generate an effective copper photocatalyst (Table 1, entries 4-7). While a 10-fold increase in Cu-1 or Cu-2 loading gave a 7% yield of 1, the corresponding homogeneous xantphos-based copper(I) photosensitizers were ineffective (Table 1, entries 8 and 9). Changing the substituents of 1,10-phenanthroline in xantphos-ligated heteroleptic copper(I) complexes (Mejfa, E. et al. A noble-metal-free system for photocatalytic hydrogen production from water. Chem. Eur. J. 19, 15972-15978 (2013)) did not improve their photocatalytic activity in the [2+2]cycloaddition with methyl acrylate (Table 1, entries 10 and 11). The well-established [Ru(bpy)3](PF6)2 photocatalyst, typically employed in the electron-transfer processes (Ischay, M. A., Lu, Z. & Yoon, T. P. [2+2]cycloadditions by oxidative visible light photocatalysis. J. Am. Chem. Soc. 132, 8572-8574 (2010)), was unable to yield the desired product (Table 1, entry 12). The homogeneous iridium triplet photosensitizers with higher transition energies (Table 1, entries 13 and 14) (Lei, T. et al. General and efficient intermolecular [2+2] photodimerization of chalcones and cinnamic acid derivatives in solution through visible-light catalysis. Angew. Chem. Int. Ed. 56, 15407-15410 (2017); Zhu, M., Zheng, C., Zhang, X. & You, S.-L. Synthesis of cyclobutane-fused angular tetracyclic spiroindolines via visible-light-promoted intramolecular dearomatization of indole derivatives. J. Am. Chem. Soc. 141, 2636-2644 (2019); Girvin, Z. C. et al. Asymmetric photochemical [2+2]-cycloaddition of acyclic vinylpyridines through ternary complex formation and an uncontrolled sensitization mechanism. J. Am. Chem. Soc. 144, 20109-20117 (2022), as well as their heterogeneous equivalents (Table 1, entries 15-18) (Wang, C., Xie, Z., deKrafft, K. E. & Lin, W. Doping metal-organic frameworks for water oxidation, carbon dioxide reduction, and organic photocatalysis. J. Am. Chem. Soc. 133, 13445-13454 (2011); Wang, C., deKrafft, K. E. & Lin, W. Pt nanoparticles@photoactive metal-organic frameworks: efficient hydrogen evolution via synergistic photoexcitation and electron injection. J. Am. Chem. Soc. 134, 7211-7214 (2012); Yu, X. & Cohen, S. M. Photocatalytic metal-organic frameworks for selective 2,2,2-trifluoroethylation of styrenes. J. Am. Chem. Soc. 138, 12320-12323 (2016); Fan, Y., Zheng, H., Labalme, S. & Lin, W. Molecular engineering of metal-organic layers for sustainable tandem and synergistic photocatalysis. J. Am. Chem. Soc. 145, 4158-4165 (2023)), are also incompatible with this reaction system, resulting in substantial substrate decomposition. Since the styrene substrate lacks a carboxylate substituent, it was not unexpected that CdSe quantum dots proved ineffective in the crossed [2+2]cycloaddition (Table 1, entry 19) (Jiang, Y., Wang, C., Rogers, C. R., Kodaimati, M. S. & Weiss, E. A. Regio- and diastereoselective intermolecular [2+2]cycloadditions photocatalysed by quantum dots. Nat. Chem. 11, 1034-1040 (2019)). Furthermore, a number of heterogeneous framework-based photocatalysts and homogeneous organic photocatalysts were investigated that could promote [2+2] dimerization of styrenes mediated by electron transfer; and none of them gave any desired products. The catalyst effect demonstrated that the binap-based copper triplet photosensitizer catalysts are capable of promoting intermolecular crossed [2+2]cycloadditions of styrenes with methyl acrylate, and successful integration of these photosensitizers on suitable MOF supports was shown to significantly boost their photocatalytic activity.
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Copper photocatalyst UiO-69-phen(binap)Cu was examined on a variety of electron-deficient alkenes to evaluate the scope of the heterogeneous photocatalytic [2+2]cycloaddition reactions (
With respect to the [2+2]cycloadditions between different styrenes, the heterogeneous copper photocatalysis proved to be more efficient (
During the photosensitization of other styrenes, the unsubstituted simple styrene was chosen as the coupling partner to determine the reaction scope. A wide range of substituted aryl groups and heterocyclic moieties were found to be compatible with this visible light photocatalysis (
The exceptional photocatalytic activity of UiO-69-phen(binap)Cu prompted us to revisit the intermolecular crossed [2+2]cycloadditions of exocyclic arylidene 4-membered rings (other than cyclobutanes) with electron-deficient alkenes (
The coupling partner scope in the heterogeneous copper photocatalytic system can be further expanded to include a wide array of styrenes that have yet to be investigated (
The significance of employing a heterogenization strategy in the design of binap-based copper photosensitizer catalysts was elucidated by control experiments comparing the photostability of Cu-2 and UiO-69-phen(binap)Cu under the standard reaction conditions without substrates (
Upon post-synthetic metalation with the cationic binap-ligated copper(I), the maximum absorption peak was observed at 449 nm, resulting from metal-to-ligand charge transfer transitions, appeared alongside the original peak at 351 nm from the MOF support (UiO-69-phen) in the solid-state absorption spectrum of UiO-69-phen(binap)Cu. Compared to other heterogeneous copper photocatalysts, the absorption profile of UiO-69-phen(binap)Cu showed the highest intensity in the region of blue-LED excitation. Notably, the phosphorescence peak of the heterogenized copper(I) species is blue-shifted by 33 nm from that of its homogeneous counterpart, with an increased excited-state lifetime at room temperature from 1.52 to 4.31 μs (
It was shown that 1-vinylnaphthalene quenches the luminescence of UiO-69-phen(binap)Cu but not UiO-69-phen(xantphos)Cu, demonstrating the superior activity of UiO-69-phen(binap)Cu in facilitating triplet energy transfer from photoexcited copper(I) to styrenes. In addition, the rate order of simple styrene was determined to be 4.28±0.40, indicating that substrate aggregation occurred prior to photoexcitation. Taken together, the following catalytic cycle may be operative (
This example detailed for the synthesis and use of well-defined crystalline MOFs to support heteroleptic copper(I) complexes in order to facilitate a series of intermolecular crossed [2+2]cycloadditions via energy transfer under visible light irradiation. The incorporation of binap-containing copper triplet photosensitizers onto the MOF organic linkers substantially improved the photostability and increased the excited-state lifetime which allowed cycloadditions of various styrenes with electron-deficient alkenes. This heterogeneous copper photocatalysis demonstrated broad substrate scope, excellent catalytic efficiency, and remarkable catalyst recyclability, as well a general approach for designing highly reactive copper photocatalysts for diverse energy-transfer-mediated organic transformations.
In particular, it was shown that associating a binap-ligated heteroleptic copper(I) complex to the linker of a microporous zirconium-based metal-organic framework (MOF) produced a highly stable and reusable heterogeneous photocatalyst with an extended excited-state lifetime. Under visible light irradiation, this copper triplet photosensitizer efficiently promoted multiple intermolecular crossed [2+2]cycloadditions, including a cycloaddition reaction of simple styrenes with electron-deficient alkenes.
Dimethyl 4,4′-(1,10-phenanthroline-3,8-diyl)dibenzoate (Li). To a solution of 3,8-dibromo-1,10-phenanthroline (3.4 g, 10 mmol, 1.0 equiv.) in dimethoxyethane (150 mL), 4-(methoxycarbonyl)phenylboronic acid (5.4 g, 30 mmol, 3.0 equiv.), Pd(dppf)Cl2 (0.732 g, 1.0 mmol, 10 mol %), and CsF (6.1 g, 40 mmol, 4.0 equiv.) were added. After stirring at 110° C. for 72 hours under N2 atmosphere, the solid was collected by centrifugation and washed with water, chloroform and cold acetone, respectively. Then resulted crude solid was further purified by Soxhlet extraction with chloroform for 48 hours. The extraction was concentrated in vacuo to give 3.1 g (7.0 mmol, 70% yield) of the title compound as a white solid.
1H NMR (CDCl3, 400 MHz): δ 9.48 (s, 2H), 8.48 (s, 2H), 8.24 (d, J=8.0 Hz, 4H), 7.94 (s, 2H), 7.88 (d, J=8.0 Hz, 4H), 3.99 (s, 6H).
13C NMR (CDCl3, 100 MHz): δ 166.7, 151.5, 149.3, 141.8, 134.9, 134.0, 130.5, 130.1, 128.6, 127.5, 127.4, 52.3.
HRMS (ESI) calculated for C28H20N2O4 [M+H]+ requires m/z 449.1496, found m/z 449.1421.
4,4′-(1,10-Phenanthroline-3,8-diyl)dibenzoic acid (L2). To a suspension of L1 (224 mg, 0.5 mmol, 1.0 equiv.) in ethanol (5.0 mL), NaOH (200 mg, 5 mmol, 10 equiv.) dissolved in water (5.0 mL) was added dropwise. The mixture was refluxed at 85° C. for 18 hours under N2 atmosphere. After cooling to room temperature, the solution was acidified to pH ˜5 with 1 M HCl. The solid was collected by filtration, washed with water, ethanol and dried in vacuo to afford 200 mg (0.475 mmol, 95% yield) of the title compound as a pale yellow solid.
1H NMR (CDCl3, 400 MHz): δ 13.12 (brs, 2H), 9.51 (d, J=2.0 Hz, 2H), 8.94 (d, J=2.0 Hz, 2H), 8.19-8.08 (m, 10H).
13C NMR (CDCl3, 100 MHz): δ 167.0, 134.2, 130.6, 130.2, 127.6, 127.5.
HRMS (ESI) calculated for C26H16N2O4 [M+H]+ requires m/z 421.1183, found m/z 421.1127.
4′-Bromo-2′,5′-dimethyl-[1,1′-biphenyl]-4-carboxylate (S1). To a suspension of 4-(methoxycarbonyl)phenylboronic acid (1.8 g, 10 mmol, 1.0 equiv.), 1,4-dioxane (48 mL), and water (12 mL), 1,4-dibromo-2,5-dimethyl-benzene (7.9 g, 30 mmol, 3.0 equiv.), Pd(dppf)Cl2 (0.37 g, 0.5 mmol, 5.0 mol %), and K2CO3 (4.1 g, 30 mmol, 3.0 equiv.) were added. After stirring at 80° C. for 8 hours under N2 atmosphere, the reaction mixture was diluted with water, and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The crude mixture was purified by flash column chromatography using hexane/ethyl acetate=10:1 as the eluent to give 2.7 g (8.6 mmol, 86% yield) of the title compound as a white solid.
1H NMR (CDCl3, 400 MHz): δ 8.08 (d, J=8.4 Hz, 2H), 7.46 (s, 1H), 7.36 (d, J=8.4 Hz, 2H), 7.08 (s, 1H), 3.94 (s, 3H), 2.39 (s, 3H), 2.19 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 166.9, 145.6, 140.0, 135.2, 134.4, 133.9, 131.7, 129.5, 129.1, 128.8, 124.1, 52.2, 22.3, 19.6.
HRMS (ESI) calculated for C16H15BrO2[M+H]+ requires m/z 319.0328, found m/z 319.0306.
Dimethyl 2′,2″,5′,5″-tetramethyl-[1,1′:4′,1″:4″,1″′-quaterphenyl]-4,4″′-dicarboxylate (S2). To a solution of S1 (7.3 g, 23 mmol, 2.3 equiv.) in dimethyl sulfoxide (40 mL), bis(pinacolato)diboron (2.5 g, 10 mmol, 1.0 equiv.), Pd(dppf)Cl2 (0.439 g, 0.6 mmol, 6.0 mol %), and K2CO3 (8.8 g, 64 mmol, 6.4 equiv.) were added. After stirring at 85° C. for 72 hours under N2 atmosphere, the reaction mixture was diluted with water, and the aqueous layer was extracted with ethyl acetate (3×60 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The crude mixture was purified by flash column chromatography using hexane/ethyl acetate=9:1 as the eluent to give 3.3 g (8.2 mmol, 82% yield) of the title compound as a white solid.
1H NMR (CDCl3, 400 MHz): δ 8.11 (d, J=8.2 Hz, 4H), 7.48 (d, J=8.2 Hz, 4H), 7.15 (s, 2H), 7.07 (s, 2H), 3.96 (s, 6H), 2.27 (s, 6H), 2.13 (s, 6H).
13C NMR (CDCl3, 100 MHz): δ 167.1, 146.7, 140.8, 139.6, 133.4, 132.1, 131.5, 131.0, 129.4, 129.3, 128.5, 52.1, 19.9, 19.4.
HRMS (ESI) calculated for C32H30O4[M+H]+ requires m/z 479.2217, found m/z 479.2195.
2′,2″,5′,5″-Tetramethyl-[1,1′:4′,1″:4″,1″′-quaterphenyl]-4,4′″-dicarboxylic acid (L3). To a solution of S2 (2.8 g, 6.0 mmol, 10 equiv.) in a mixed solvent of tetrahydrofuran (96 mL), methanol (24 mL), and water (24 mL), LiOH·H2O (2.5 g, 60 mmol, 10 equiv.) was added. After stirring at room temperature overnight, the solution was acidified to pH ˜5 with 1 M HCl. Then solvent was removed. The resulted solid was collected via filtration and washed with water and dried in vacuo to afford 2.4 g (5.3 mmol, 89% yield) of the title compound as a white solid.
1H NMR (DMSO-d6, 400 MHz): δ 12.99 (brs, 2H), 8.03 (d, J=8.2 Hz, 4H), 7.55 (d, J=8.2 Hz, 4H), 7.20 (s, 2H), 7.08 (s, 2H), 2.25 (s, 6H), 2.08 (s, 6H).
13C NMR (DMSO-d6, 100 MHz): δ 167.2, 145.6, 140.3, 139.2, 132.8, 131.8, 131.3, 130.8, 129.3, 129.2, 19.6, 19.0.
HRMS (ESI) calculated for C30H26O4[M+H]+ requires m/z 451.1904, found m/z 451.1837.
Cu-1. To a 50-mL flame-dried Schlenk flask cooled under N2, Cu(MeCN)4PF6 (93 mg, 0.25 mmol), [1,1′-binaphthalene]-2,2′-diyl)bis(diphenylphosphane) (rac-binap) (156 mg, 0.25 mmol, 1.0 equiv.), and dichloromethane (20 mL) were added sequentially. After stirring at room temperature for 1 hour, Li (105 mg, 0.25 mmol, 1.0 equiv.) in 15 mL of mixed solvents of dichloromethane and dimethylformamide (5:1 v/v) was added in dropwise. Then, the whole solution was stirred at room temperature overnight. After the reaction was completed, dichloromethane was removed in vacuo. The residue was diffused into diethyl ether (80 mL) dropwise and the resulted yellow solid (229 mg, 0.183 mmol, 73% yield) was collected via filtration, washed by diethyl ether for several times and dried in vacuo.
1H NMR (CDCl3, 400 MHz): δ 8.90 (s, 2H), 8.53 (s, 2H), 8.36 (s, 2H), 8.23 (d, J=8.2 Hz, 4H), 7.63 (d, J=8.2 Hz, 2H), 7.59-7.51 (m, 6H), 7.46 (t, J=7.4 Hz, 2H), 7.36-7.11 (m, 14H), 7.08-7.00 (m, 4H), 6.92 (t, J=7.4 Hz, 2H), 6.78 (d, J=8.4 Hz, 2H), 6.70 (t, J=7.4 Hz, 4H), 4.02 (s, 6H).
31P NMR (CDCl3, 162 MHz): δ 1.7, −135.4-−153.0 (m, 1P).
13C NMR (CDCl3, 100 MHz): δ 166.6, 148.8, 142.2 (virtual triplet, JPC=1.6 Hz), 139.9, 139.8 (virtual triplet, JPC=10.0 Hz), 136.7, 135.9, 134.1 (virtual triplet, JPC=4.2 Hz), 133.9 (virtual triplet, JPC=9.2 Hz), 133.20, 133.15 (virtual triplet, JPC=8.2 Hz), 131.7 (virtual triplet, JPC=17.7 Hz), 130.7, 130.3 (virtual triplet, JPC=13.8 Hz), 130.0, 129.3 (virtual triplet, JPC=5.0 Hz), 129.1 (virtual triplet, JPC=2.9 Hz), 128.7, 128.3 (virtual triplet, JPC=16.5 Hz), 128.2, 127.7 (virtual triplet, JPC=5.3 Hz), 127.5, 127.4 (virtual triplet, JPC=3.5 Hz), 127.23 (virtual triplet, JPC=29.9 Hz), 127.21 52.5.
FT-IR (film): 2923, 1717, 1431, 1280, 1106, 838, 748, 558 cm−1.
HRMS (ESI) calculated for [C72H52CuN2O4P2]+ requires m/z 1133.2693, found m/z 1133.2693.
Cu-2. To a 50-mL flame-dried Schlenk flask cooled under N2, Cu(MeCN)4PF6 (93 mg, 0.25 mmol), dichloromethane (20 mL), and rac-binap (156 mg, 0.25 mmol, 1.0 equiv.) were added sequentially. After stirring at room temperature for 1 hour, L2 (112 mg, 0.25 mmol, 1.0 equiv.) in dichloromethane and dimethylformamide (5:1 v/v) was added in dropwise. Then, the whole solution was stirred at room temperature overnight. After the reaction was completed, dichloromethane was removed in vacuo. The residue was diffused into diethyl ether (50 mL) dropwise and the resulted yellow solid (276 mg, 0.215 mmol, 86% yield) was collected via filtration, washed by diethyl ether for several times and dried in vacuo.
1H NMR (DMSO-d6, 400 MHz): δ 13.2 (brs, 2H), 9.27 (s, 2H), 8.78 (s, 2H), 8.40 (s, 2H), 8.16 (d, J=7.6 Hz, 4H), 7.85-7.66 (m, 8H), 7.49-7.06 (m, 20H), 6.91 (s, 2H), 6.76-6.65 (m, 6H).
31P NMR (DMSO-d6, 162 MHz): δ 2.3, −135.4-−153.0 (m, 1P).
FT-IR (film): 2973, 1689, 1276, 1069, 838, 743, 693 cm−1.
HRMS (ESI) calculated for [C70H48CuN2O4P2]+ requires m/z 1105.2380, found m/z 1105.2373.
Cu-3. To a 50-mL flame-dried Schlenk flask cooled under N2, Cu(MeCN)4PF6 (93 mg, 0.25 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) (xantphos) (146 mg, 0.25 mmol, 1.0 equiv.), and dichloromethane (20 mL) were added sequentially. After stirring at room temperature for 1 hour, L1 (105 mg, 0.25 mmol, 1.0 equiv.) in 15 mL of mixed solvents of dichloromethane and dimethylformamide (2:1 v/v) was added in dropwise. Then, the whole solution was stirred at room temperature overnight. After the reaction was completed, dichloromethane was removed in vacuo. The residue was diffused into diethyl ether (80 mL) dropwise and the resulted orange solid (216 mg, 0.18 mmol, 72% yield) was collected via filtration, washed by diethyl ether for several times and dried in vacuo.
1H NMR (DMSO-d6, 400 MHz): δ 9.13 (s, 2H), 8.69 (s, 2H), 8.30 (s, 2H), 8.13 (d, J=8.4 Hz, 4H), 7.91 (d, J=7.2 Hz, 2H), 7.61 (d, J=8.4 Hz, 4H), 7.28 (t, J=7.6 Hz, 6H), 7.13 (t, J=7.6 Hz, 8H), 7.04-6.91 (m, 8H), 6.64-6.54 (m, 2H), 3.93 (s, 6H), 1.70 (s, 6H).
31P NMR (DMSO-d6, 162 MHz): δ −11.4, −124.7-159.9 (m, 1P).
13C NMR (DMSO-d6, 100 MHz): δ 165.8, 154.5 (virtual triplet, JPC=6.4 Hz), 147.4, 141.7 (virtual triplet, JPC=1.8 Hz), 139.7, 135.9, 135.5, 134.0, 132.5 (virtual triplet, JPC=8.0 Hz), 131.0, 130.7 (virtual triplet, JPC=17.0 Hz), 130.1 (two carbon signals overlapped), 130.0, 129.4, 128.8 (virtual triplet, JPC=4.7 Hz), 128.2, 127.9, 127.7, 125.6, 119.1 (virtual triplet, JPC=13.6 Hz), 52.5, 36.0, 27.7.
FT-IR (film): 2933, 1708, 1231, 845, 746, 670 cm−1.
HRMS (ESI) calculated for [C67H52CuN2O5P2]+ requires m/z 1089.2642, found m/z 1089.2258.
Cu-4. To a 50-mL flame-dried Schlenk flask cooled under N2, Cu(MeCN)4PF6 (93 mg, 0.25 mmol), xantphos (146 mg, 0.25 mmol, 1.0 equiv.), and dichloromethane (20 mL) were added sequentially. After stirring at room temperature for 1 hour, L2 (105 mg, 0.25 mmol, 1.0 equiv.) in 15 mL of mixed solvents of dichloromethane and dimethylformamide (2:1 v/v) was added in dropwise. Then, the whole solution was stirred at room temperature overnight. After the reaction was completed, dichloromethane was removed in vacuo. The residue was diffused into diethyl ether (80 mL) dropwise and the resulted orange solid (216 mg, 0.18 mmol, 72% yield) was collected via filtration, washed by diethyl ether for several times and dried in vacuo.
1H NMR (DMSO-d6, 400 MHz): δ 13.2 (brs, 2H), 9.12 (s, 2H), 8.70 (s, 2H), 8.30 (s, 2H), 8.12 (d, J=8.4 Hz, 4H), 7.89 (s, 2H), 7.60 (s, 2H), 7.42-6.83 (m, 24H), 6.58 (d, J=6.9 Hz, 2H), 1.69 (s, 6H).
31P NMR (DMSO-d6, 162 MHz): δ −11.4, −135.4-−153.0 (m, 1P).
FT-IR (film): 2985, 1705, 1226, 842, 743, 693 cm−1.
HRMS (ESI) calculated for [C65H48CuN2O5P2]+ requires m/z 1061.2329, found m/z 1061.2329.
ZrCl4 (179 mg, 0.77 mmol), 4,4′-(1,10-phenanthroline-3,8-diyl)dibenzoic acid (L2) (50 mg, 0.12 mmol), terphenyl dicarboxylic acid (L3) (270 mg, 0.60 mmol), and trifluoroacetic acid (0.4 mL) were ultrasonically dispersed in dimethylformamide (34 mL). The resulting solution was heated to 100° C. in a 50-mL glass tube for 3 days. After cooling to room temperature, the supernatant was decanted and the solid was washed five times with dimethylformamide and acetone. UiO-69-phen was then collected by filtration and dried in air to give a white solid (389 mg, 60% yield based on linkers). The product (2 mg) was digested in a mixture of a saturated K3PO4/D2O solution and DMSO-d6 (0.6 mL, 1:2 v/v) and subjected to 1H NMR analysis. The ratio of L2 and L3 was found to be 1:5. The chemical formula of UiO-69-phen was determined to be Zr6O4(OH)4(L2)(L3)5-4.0DMF based on NMR digestion data and TGA.
UiO-69-phen (30.0 mg, 5.6 μmol based on L2) was immersed in a 2-mL dichloromethane solution of [Cu (MeCN)4](PF6) (10.4 mg, 28 μmol) and stirred under N2 atmosphere at 60° C. for 4 hours. After cooling to room temperature, the supernatant was decanted and the solid was washed five times with dimethylformamide and acetone. UiO-69-phenCu was then collected by filtration and dried in air to give a green solid (22.7 mg, 93% yield). ICP-AES analysis indicated a Zr/Cu ratio of 6:1. The chemical formula of UiO-69-phenCu was determined to be {Zr6O4 (OH)4(L2)(L3)5[Cu(CH3CN)2PF6]}·0.4.4DMF based on ICP-AES and TGA.
UiO-69-phen (30.0 mg, 5.6 mol based on L2) was immersed in a 2-mL dichloromethane solution of [Cu(xantphos)(MeCN)2](PF6) (24.3 mg, 28 mol) and stirred under N2 atmosphere at room temperature for 9 hours. After post-synthetic metalation, the supernatant was decanted and the solid was washed five times with DMF and acetone. UiO-69-phen(xantphos)Cu was then collected by filtration and dried in air to give a yellow solid (30.9 mg, 91% yield). ICP-AES analysis indicated a Zr/Cu ratio of 6:1. The product (2 mg) was digested in a solution of D3PO4/D2O/DMSO-d6 (1:1:5 v/v/v) and subjected to 1H NMR analysis. The ratio of Cu-3 and L3 was found to be 1:5. The chemical formula of UiO-69-phen(xantphos)Cu was determined to be
{Zr6O4(OH)4(L2)(L3)5[Cu(xantphos)PF6]}·4.9DMF based on NMR digestion data and TGA.
UiO-69-phen (300 mg, 56 μmol based on L2) was immersed in a 20-mL dichloromethane solution of [Cu(binap)(MeCN)2](PF6) (256 mg, 0.28 mmol) and stirred under N2 atmosphere at room temperature for 9 hours. After post-synthetic metalation, the supernatant was decanted and the solid was washed five times with DMF and acetone. UiO-69-phen(binap)Cu was then collected by filtration and dried in air to give a yellow solid (312 mg, 94% yield). ICP-AES analysis indicated a Zr/Cu ratio of 6:1. The product (2 mg) was digested in a solution of D3PO4/D2O/DMSO-d6 (1:1:5 v/v/v) and subjected to 1H NMR analysis. The ratio of Cu-2 and L3 was found to be 1:5. The chemical formula of UiO-69-phen(binap)Cu was determined to be {Zr6O4(OH)4(L2)(L3)5[Cu(binap)PF6]}·6.0DMF based on NMR digestion data and TGA.
Based on TGA (
3-(Naphthalen-2-ylmethylene)oxetane. The title compound was synthesized according to the literature reported method2 using the corresponding phosphonium bromide (9.7 g, 20 mmol, 1.0 equiv.), oxetan-3-one (1.4 mL, 24 mmol, 1.2 equiv.), tBuOK (2.2 g, 20 mmol, 1.0 equiv.), and tetrahydrofuran (200 mL). After the completion of the reaction, the crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1 v/v) as the eluent to give 2.7 g (13.6 mmol, 68% yield) of the title compound as a white solid.
1H NMR (CDCl3, 400 MHz): δ 7.84-7.72 (m, 3H), 7.52-7.40 (m, 3H), 7.10 (dd, J=8.6, 1.8 Hz, 1H), 6.31-6.20 (m, 1H), 5.72-5.63 (m, 2H), 5.48-5.39 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 137.4, 133.50, 133.49, 132.2, 128.4, 127.9, 127.6, 126.4, 126.3, 126.0, 124.6, 119.8, 80.5, 80.3.
HRMS (EI) calculated for [C14H12O]+ requires m/z 196.0883, found m/z 196.0884.
3-([1,1′-Biphenyl]-4-ylmethylene)oxetane. The title compound was synthesized according to the literature reported method2 using the corresponding phosphonium bromide (1.2 g, 2.0 mmol, 1.0 equiv.), oxetan-3-one (180 μL, 3.0 mmol, 1.5 equiv.), tBuOK (0.224 g, 2.0 mmol, 1.0 equiv.), and tetrahydrofuran (20 mL). After the completion of the reaction, the crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1 v/v) as the eluent to give 0.305 g (1.38 mmol, 69% yield) of the title compound as a white solid.
1H NMR (CDCl3, 400 MHz): δ 7.62-7.53 (m, 4H), 7.47-7.40 (m, 2H), 7.37-7.31 (m, 1H), 7.07 (d, J=8.4 Hz, 2H), 6.18-6.08 (m, 1H), 5.66-5.55 (m, 2H), 5.45-5.35 (m, 2H)
13C NMR (CDCl3, 100 MHz): δ 140.5, 139.6, 137.2, 135.0, 128.8, 127.5, 127.4, 126.9, 119.3, 80.40, 80.27.
HRMS (EI) calculated for [C16H14O]+ requires m/z 222.1039, found m/z 222.1041.
To a 25-mL flame-dried Schlenk flask cooled under N2, 3-(4-bromobenzylidene)oxetane (222 mg, 1.0 mmol, 1.0 equiv.) was added to 4 mL of tetrahydrofuran (0.25 M). After cooled to −78° C., nBuLi (2.5 M in THF, 440 μL, 1.1 equiv.) was injected dropwise. The resulting solution was stirred at −78° C. for 1 hour and then dimethylacetamide (50 mmol, 4.6 mL) was added. The system was slowly warmed to room temperature and stirred at ambient temperature for another 1 hour. The reaction was then quenched by saturated aqueous NH4Cl solution, extracted with ethyl acetate (3×30 mL). The combined organic layers were washed by water, brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography using hexanes/ethyl acetate (7:1 v/v) as the eluent to give 58 mg (0.31 mmol, 31% yield) of 1-(4-(oxetan-3-ylidenemethyl)phenyl)ethan-1-one as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.92 (d, J=8.4 Hz, 2H), 7.07 (d, J=8.4 Hz, 2H), 6.19-6.14 (m, 1H), 5.62-5.56 (m, 2H), 5.44-5.37 (m, 2H), 2.59 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 197.4, 140.8, 140.5, 135.3, 128.9, 127.1, 119.0, 80.3, 80.1, 26.5.
HRMS (EI) calculated for [C12H12O2]+ requires m/z 188.0832, found m/z 188.0835.
To a 25-mL flame-dried Schlenk flask cooled under N2, 3-(4-bromobenzylidene)oxetane (222 mg, 1.0 mmol, 1.0 equiv.) was added to 4 mL of tetrahydrofuran (0.25 M). After cooled to −78° C., nBuLi (2.5 M in THF, 440 μL, 1.1 equiv.) was injected dropwise. The resulting solution was stirred at −78° C. for 1 hour and then dimethylformamide (50 mmol, 3.9 mL) was added. The system was slowly warmed to room temperature and stirred at ambient temperature for another 1 hour. The reaction was then quenched by saturated aqueous NH4Cl solution, extracted with ethyl acetate (3×30 mL). The combined organic layers were washed by water, brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography using hexanes/ethyl acetate (7:1 v/v) as the eluent to give 89 mg (0.51 mmol, 51% yield) of 4-(oxetan-3-ylidenemethyl)benzaldehyde as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.98 (s, 1H), 7.84 (d, J=8.4 Hz, 2H), 7.14 (d, J=8.4 Hz, 2H), 6.22-6.16 (m, 1H), 5.64-5.57 (m, 2H), 5.45-5.38 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 191.5, 141.9, 141.7, 134.6, 130.2, 127.5, 119.0, 80.3, 80.1.
HRMS (EI) calculated for [C11H10O2]+ requires m/z 174.0675, found m/z 174.0679.
To a 50-mL flame-dried Schlenk flask cooled under N2, the phosphonium bromide (2.9 g, 6.0 mmol, 1.2 equiv.) was added to 15 mL of tetrahydrofuran. After cooled to 0° C., nBuLi (2.5 M in THF, 2.8 mL, 1.4 equiv.) was injected dropwise. The resulting solution was stirring at 0° C. for 1 hour and then cyclohexanone (5.0 mmol, 518 μL, 1.0 equiv.) in 5 mL of tetrahydrofuran was added dropwise. The system was warmed to room temperature and stirred at ambient temperature for another 18 hour. The reaction was then quenched by saturated aqueous NH4Cl solution and extracted with ethyl acetate (3×40 mL). The combined organic layers were washed by water, brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography using hexanes as the eluent to give 0.697 g (3.15 mmol, 63% yield) of 2-(cyclohexylidenemethyl)naphthalene as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.83-7.71 (m, 3H), 7.65-7.60 (m, 1H), 7.48-7.38 (m, 2H), 7.38-7.32 (m, 1H), 6.37 (s, 1H), 2.49-2.40 (m, 2H), 2.35-2.26 (m, 2H), 1.73-1.54 (m, 6H).
13C NMR (CDCl3, 100 MHz): δ 144.0, 135.9, 133.4, 131.8, 127.8, 127.7, 127.5, 127.4, 127.1, 125.9, 125.3, 122.0, 37.7, 29.6, 28.6, 27.9, 26.7.
HRMS (EI) calculated for [C17H18]+ requires m/z 222.1403, found m/z 222.1406.
Trans-methyl 2-(naphthalen-1-yl)cyclobutane-1-carboxylate (1). The title compound was synthesized according to the General Procedure A using 1-vinylnaphthalene (30.7 mg, 0.2 mmol) and methyl acrylate (91 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 35.2 mg (0.146 mmol, 73% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.96-7.92 (m, 1H), 7.86-7.82 (m, 1H), 7.74-7.70 (m, 1H), 7.51-7.44 (m, 4H), 4.44 (q, J=9.2 Hz, 1H), 3.69 (s, 3H), 3.57-3.48 (m, 1H), 2.63-2.52 (m, 1H), 2.49-2.38 (m, 1H), 2.27-2.07 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 174.9, 139.0, 133.7, 131.3, 128.7, 127.0, 125.8, 125.6, 125.4, 123.9, 122.6, 51.8, 43.1, 41.0, 27.0, 22.0.
HRMS (EI) calculated for [C16H16O2]+ requires m/z 240.1145, found m/z 240.1148.
Trans-tert-butyl 2-(naphthalen-1-yl)cyclobutane-1-carboxylate (2). The title compound was synthesized according to the General Procedure A using 1-vinylnaphthalene (30.9 mg, 0.2 mmol) and tert-butyl acrylate (145 ptL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 46.1 mg (0.164 mmol, 80% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.01-7.96 (m, 1H), 7.86-7.82 (m, 1H), 7.74-7.70 (m, 1H), 7.50-7.44 (m, 4H), 4.38 (q, J=9.2 Hz, 1H), 3.43-3.33 (m, 1H), 2.58-2.49 (m, 1H), 2.42-2.32 (m, 1H), 2.25-2.06 (m, 2H), 1.44 (s, 9H).
13C NMR (CDCl3, 100 MHz): δ 173.9, 139.5, 133.7, 131.4, 128.6, 126.8, 125.7, 125.5, 125.4, 124.1, 122.7, 80.3, 44.8, 40.8, 28.1, 26.6, 21.9.
HRMS (EI) calculated for [C19H22O2]+ requires m/z 282.1614, found m/z 282.1624.
Trans-benzyl 2-(naphthalen-1-yl)cyclobutane-1-carboxylate (3). The title compound was synthesized according to the General Procedure A using 1-vinylnaphthalene (30.9 mg, 0.2 mmol) and benzyl acrylate (162 mg, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 46.4 mg (0.146 mmol, 73% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.97-7.91 (m, 1H), 7.88-7.82 (m, 1H), 7.76-7.68 (m, 1H), 7.51-7.43 (m, 4H), 7.35-7.26 (m, 5H), 5.23-5.06 (m, 2H), 4.56-4.38 (m, 1H), 3.64-3.47 (m, 1H), 2.65-2.39 (m, 2H), 2.29-2.10 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 174.3, 139.0, 136.0, 133.7, 131.3, 128.7, 128.5, 128.1, 128.0, 127.0, 125.8, 125.6, 125.4, 123.9, 122.7, 66.3, 43.5, 40.9, 26.9, 22.0.
HRMS (EI) calculated for [C22H20O2]+ requires m/z 316.1458, found m/z 316.1467.
Trans-3,3,3-trifluoro-2-(trifluoromethyl)propyl-2-(naphthalen-1-yl)cyclobutane-1-carboxylate (4). The title compound was synthesized according to the General Procedure A using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and 1,1,1,3,3,3-hexafluoropropan-2-yl acrylate (222 mg, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 45.0 mg (0.120 mmol, 60% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.94-7.83 (m, 2H), 7.75 (d, J=8.0 Hz, 1H), 7.53-7.44 (m, 3H), 7.43-7.38 (m, 1H), 5.90-5.72 (m, 1H), 4.52 (q, J=9.2 Hz, 1H), 3.77-3.64 (m, 1H), 2.75-2.61 (m, 1H), 2.54-2.32 (m, 2H), 2.29-2.16 (m, 1H).
19F NMR (376 MHz, CDCl3): δ −73.3.
13C NMR (CDCl3, 100 MHz): δ 171.1, 138.0, 133.8, 131.0, 128.8, 127.4, 126.0, 125.8, 125.4, 123.6, 122.5, 120.4 (q, J=272.2 Hz), 66.6 (p, J=34.7 Hz), 42.2, 40.7, 27.1, 22.2.
HRMS (EI) calculated for [C18H14F6O2]+ requires m/z 376.0893, found m/z 376.0893.
Trans-prop-2-yn-1-yl 2-(naphthalen-1-yl)cyclobutane-1-carboxylate (5). The title compound was synthesized according to the General Procedure A using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and prop-2-yn-1-yl acrylate (110 mg, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 38.1 mg (0.144 mmol, 72% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.98-7.91 (m, 1H), 7.87-7.82 (m, 1H), 7.76-7.70 (m, 1H), 7.52-7.42 (m, 4H), 4.70 (qd, J=15.6, 2.4 Hz, 2H), 4.48 (q, J=9.2 Hz, 1H), 3.63-3.49 (m, 1H), 2.65-2.54 (m, 1H), 2.51-2.38 (m, 2H), 2.31-2.10 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 173.6, 138.8, 133.8, 131.2, 128.7, 127.0, 125.9, 125.6, 125.4, 123.8, 122.6, 77.7, 74.9, 52.1, 43.0, 40.8, 27.0, 22.0.
HRMS (EI) calculated for [C18H16O2]+ requires m/z 264.1145, found m/z 264.1153.
Trans-N,N-dimethyl-2-(naphthalen-1-yl)cyclobutane-1-carboxamide (6). The title compound was synthesized according to the General Procedure A using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and N,N-dimethylacrylamide (110 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (3:1 v/v) as the eluent to give 37.0 mg (0.146 mmol, 73% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.11-8.05 (m, 1H), 7.86-7.80 (m, 1H), 7.71 (d, J=7.6 Hz, 1H), 7.52-7.38 (m, 4H), 4.70-4.57 (m, 1H), 3.59-3.47 (m, 1H), 2.94 (s, 3H), 2.76 (s, 3H), 2.54-2.45 (m, 1H), 2.41-2.17 (m, 3H).
13C NMR (CDCl3, 100 MHz): δ 173.6, 140.1, 133.8, 131.5, 128.5, 126.8, 125.7, 125.6, 125.4, 124.2, 122.6, 43.7, 39.2, 36.7, 35.6, 25.3, 22.3.
HRMS (EI) calculated for [C17H19NO]+ requires m/z 253.1461, found m/z 253.1471.
1-(2-(Naphthalen-1-yl)cyclobutyl)propan-1-one (7). The title compound was synthesized according to the General Procedure A using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and pent-1-en-3-one (89 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (15:1 v/v) as the eluent to give 31.9 mg (0.134 mmol, 67% yield, 6.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.01-7.91 (m, 1H), 7.89-7.81 (m, 1H), 7.76-7.70 (m, 1H), 7.52-7.42 (m, 4H), 4.48-4.35 (m, 1H), 3.69-3.57 (m, 1H), 2.53-2.29 (m, 4H), 2.23-2.10 (m, 2H), 1.03 (t, J=7.2 Hz, 3H).
13C NMR (CDCl3, 100 MHz): δ 211.7, 139.5, 133.8, 131.3, 128.7, 126.9, 125.9, 125.7, 125.4, 123.8, 122.5, 50.4, 39.5, 34.6, 26.1, 21.5, 7.6.
HRMS (EI) calculated for [C17H18O4]+ requires m/z 238.1352, found m/z 238.1354.
Dimethyl 3-(naphthalen-1-yl)cyclobutane-1,2-dicarboxylate (8). The title compound was synthesized according to the General Procedure A using 1-vinylnaphthalene (30.8 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1 v/v) as the eluent to give 52.0 mg (0.174 mmol, 87% yield, 2.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.98 (d, J=8.4 Hz, 0.34H), 7.91-7.81 (m, 1.66H), 7.77-7.71 (m, 1H), 7.55-7.42 (m, 4H), 4.83 (q, J=9.2 Hz, 0.34H), 4.31 (q, J=9.6 Hz, 0.66H), 4.13-3.95 (m, 0.34H), 3.84-3.76 (m, 1.68H), 3.75-3.62 (m, 4.30H), 3.60-3.49 (m, 0.66H), 3.16-3.06 (m, 0.34H), 2.93-2.83 (m, 1.68H), 2.73-2.64 (m, 0.34H), 2.33 (q, J=10.4 Hz, 0.66H).
13C NMR (CDCl3, 100 MHz): δ 174.8, 173.5, 173.2, 171.7, 137.5, 134.9, 133.7, 133.5, 131.6, 131.2, 128.8, 128.5, 127.6, 127.4, 126.0, 125.7, 125.6, 125.5, 125.2, 123.7, 123.5, 123.4, 123.0, 52.17, 52.14, 52.07, 51.0, 47.3, 45.7, 37.3, 37.1, 36.7, 36.5, 30.7, 26.5.
HRMS (EI) calculated for [C18H18O4]+ requires m/z 298.1200, found m/z 298.1202.
Dimethyl 3-(naphthalen-2-yl)cyclobutane-1,2-dicarboxylate (9). The title compound was synthesized according to the General Procedure A using 2-vinylnaphthalene (30.9 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 48.9 mg (0.164 mmol, 82% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.86-7.73 (m, 3H), 7.71-7.64 (m, 1H), 7.51-7.38 (m, 2.60H), 7.33 (dd, J=8.4, 1.6 Hz, 0.40H), 4.21-4.08 (m, 0.40H), 3.98-3.86 (m, 0.40H), 3.84-3.68 (m, 5.80H), 3.65-3.57 (m, 0.60H), 3.51-3.40 (m, 0.60H), 3.19 (s, 1.20H), 2.90-2.79 (m, 0.40H), 2.77-2.63 (m, 1H), 2.50-2.38 (m, 0.60H).
13C NMR (CDCl3, 100 MHz): δ 174.6, 173.6, 173.1, 171.6, 139.5, 137.3, 133.3, 133.2, 132.4, 128.3, 127.82, 127.78, 127.7, 127.6, 127.5, 126.2, 126.0, 125.8, 125.74, 125.66, 125.0, 124.9, 52.08, 52.05, 51.4, 47.5, 46.5, 40.0, 39.8, 36.8, 36.6, 29.4, 27.7.
HRMS (EI) calculated for [C18H18O4]+ requires m/z 298.1200, found m/z 298.1208.
Dimethyl 3-(phenanthren-9-yl)cyclobutane-1,2-dicarboxylate (10). The title compound was synthesized according to the General Procedure A using 9-vinylphenanthrene (40.8 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 45.3 mg (0.130 mmol, 65% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.76-8.67 (m, 1H), 8.67-8.60 (m, 1H), 8.05-7.98 (m, 0.40H), 7.94-7.85 (m, 1.60H), 7.73 (s, 0.60H), 7.69-7.54 (m, 4.40H), 4.92-4.73 (m, 0.40H), 4.37-4.25 (m, 0.60H), 4.11-4.04 (m, 0.40H), 3.96-3.88 (m, 0.60H), 3.82 (s, 1.20H), 3.76-3.71 (m, 3.60H), 3.70-3.65 (m, 0.40H), 3.64-3.55 (m, 0.60H), 3.31-3.19 (m, 0.40H), 2.97-2.88 (m, 0.60H), 2.86 (s, 1.20H), 2.77-2.67 (m, 0.40H), 2.41-2.27 (m, 0.60H).
13C NMR (CDCl3, 100 MHz): δ 174.8, 173.5, 173.3, 171.7, 135.7, 133.1, 131.5, 131.3, 130.7, 130.4, 130.3, 129.8, 129.7, 129.5, 128.7, 128.6, 126.8, 126.7, 126.60, 126.57, 126.55, 126.5, 126.34, 126.31, 124.7, 124.5, 124.1, 123.9, 123.3, 122.9, 122.39, 122.36, 52.21, 52.19, 52.1, 51.0, 47.4, 45.2, 37.6, 37.2, 37.1, 36.81, 30.78, 26.3.
HRMS (EI) calculated for [C22H20O4]+ requires m/z 348.1356, found m/z 348.1365.
Dimethyl 3-([1,1′-biphenyl]-4-yl)cyclobutane-1,2-dicarboxylate (11). The title compound was synthesized according to the General Procedure A using 4-vinyl-1,1′-biphenyl (36.0 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 51.9 mg (0.160 mmol, 80% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.61-7.52 (m, 4H), 7.46-7.40 (m, 2H), 7.38-7.27 (m, 3H), 4.08-3.97 (m, 0.40H), 3.92-3.84 (m, 0.40H), 3.79-3.71 (m, 5.20H), 3.70-3.63 (m, 0.60H), 3.58-3.50 (m, 0.60H), 3.47-3.37 (m, 0.60H), 3.29 (s, 1.20H), 2.79-2.59 (m, 1.40H), 2.43-2.31 (m, 0.60H).
13C NMR (CDCl3, 100 MHz): δ 174.6, 173.6, 173.1, 171.6, 141.2, 140.8, 140.6, 139.8, 139.7, 138.9, 128.7, 127.8, 127.24, 127.21, 127.02, 127.00, 126.91, 126.88, 52.09, 52.06, 51.4, 47.6, 46.5, 39.6, 39.4, 36.8, 36.6, 29.4, 27.8.
HRMS (EI) calculated for [C20H20O4]+ requires m/z 324.1356, found m/z 324.1365.
Dimethyl 3-(4-formylphenyl)cyclobutane-1,2-dicarboxylate (12). The title compound was synthesized according to the General Procedure A using 4-vinylbenzaldehyde (26.4 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 28.2 mg (0.102 mmol, 51% yield, 1.9:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 10.00 (s, 0.65H), 9.99 (s, 0.35H), 7.91-7.78 (m, 2H), 7.50-7.42 (m, 1.35H), 7.39 (d, J=8.0 Hz, 0.65H), 4.14-4.03 (m, 0.35H), 3.95-3.86 (m, 0.35H), 3.80-3.69 (m, 5.95H), 3.57-3.38 (m, 1.30H), 3.28 (s, 1.05H), 2.80-2.59 (m, 1.35H), 2.41-2.30 (m, 0.65H).
13C NMR (CDCl3, 100 MHz): δ 191.84, 191.83, 174.2, 173.4, 172.7, 171.2, 149.1, 147.1, 135.1, 130.1, 129.7, 128.0, 127.2, 127.1, 52.24, 52.20, 52.17, 51.5, 47.2, 46.4, 39.9, 39.5, 36.8, 36.6, 29.0, 27.5.
HRMS (EI) calculated for [C15H16O5]+ requires m/z 276.0992, found m/z 276.1003.
Dimethyl 3-(4-acetylphenyl)cyclobutane-1,2-dicarboxylate (13). The title compound was synthesized according to the General Procedure A using 1-(4-vinylphenyl)ethan-1-one (32.4 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (20:1 v/v) as the eluent to give 31.9 mg (0.110 mmol, 55% yield, 1.9:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.96-7.87 (m, 2H), 7.40-7.34 (m, 1.34H), 7.32 (d, J=8.3 Hz, 0.66H), 4.11-3.99 (m, 0.34H), 3.97-3.84 (m, 0.34H), 3.78-3.66 (m, 5.66H), 3.56-3.38 (m, 1.32H), 3.29 (s, 1.02H), 2.78-2.55 (m, 4.66H), 2.41-2.29 (m, 0.66H).
13C NMR (CDCl3, 100 MHz): δ 197.71, 197.68, 174.3, 173.4, 172.8, 171.3, 147.5, 145.5, 135.8, 128.7, 128.4, 127.6, 126.8, 126.6, 52.20, 52.17, 52.1, 51.5, 47.3, 46.3, 39.7, 39.4, 36.8, 36.6, 29.1, 27.5, 26.60, 26.58.
HRMS (EI) calculated for [C16H18O5]+ requires m/z 290.1149, found m/z 290.1156.
Dimethyl 3-(quinolin-6-yl)cyclobutane-1,2-dicarboxylate (14). The title compound was synthesized according to the General Procedure A using 6-vinylquinoline (31.1 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (6:1→3:1 v/v) as the eluent to give 31.7 mg (0.106 mmol, 53% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.96-8.83 (m, 1H), 8.17-8.11 (m, 1H), 8.08 (d, J=8.7 Hz, 0.55H), 8.04 (d, J=8.7 Hz, 0.45H), 7.71-7.64 (m, 1.55H), 7.57 (dd, J=8.7, 2.1 Hz, 0.45H), 7.45-7.37 (m, 1H), 4.25-4.15 (m, 0.45H), 4.00-3.90 (m, 0.45H), 3.88-3.72 (m, 5.65H), 3.65-3.58 (m, 0.55H), 3.50-3.42 (m, 0.55H), 3.20 (s, 1.35H), 2.92-2.81 (m, 0.45H), 2.78-2.68 (m, 1H), 2.49-2.40 (m, 0.55H).
13C NMR (CDCl3, 100 MHz): δ 174.4, 173.5, 172.9, 171.5, 150.24, 150.17, 147.4, 140.4, 138.3, 136.0, 135.9, 129.74, 129.68, 129.3, 128.6, 128.1, 128.0, 125.5, 124.8, 124.5, 121.4, 121.3, 52.18, 52.16, 52.1, 51.5, 47.5, 46.5, 39.8, 39.5, 36.8, 36.6, 29.3, 27.6.
HRMS (EI) calculated for [C17H17NO4]+ requires m/z 299.1152, found m/z 299.1155.
Dimethyl 3-(isoquinolin-6-yl)cyclobutane-1,2-dicarboxylate (15). The title compound was synthesized according to the General Procedure A using 6-vinylisoquinoline (31.1 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (6:1-3:1 v/v) as the eluent to give 29.9 mg (0.100 mmol, 50% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.95-8.81 (m, 1H), 8.19-8.01 (m, 2H), 7.72-7.63 (m, 1.60H), 7.57 (dd, J=8.8, 2.1 Hz, 0.40H), 7.45-7.35 (m, 1H), 4.26-4.14 (m, 0.40H), 4.01-3.90 (m, 0.40H), 3.88-3.72 (m, 5.80H), 3.65-3.58 (m, 0.60H), 3.52-3.42 (m, 0.60H), 3.20 (s, 1.20H), 2.89-2.81 (m, 0.40H), 2.78-2.66 (m, 1H), 2.51-2.38 (m, 0.60H).
13C NMR (CDCl3, 100 MHz): δ 174.4, 173.5, 172.9, 171.5, 150.3, 150.2, 147.4, 140.4, 138.2, 136.0, 135.9, 129.73, 129.68, 129.3, 128.6, 128.1, 128.0, 125.5, 124.8, 121.4, 121.3, 52.19, 52.16, 52.1, 51.5, 47.5, 46.5, 39.8, 39.5, 36.8, 36.6, 29.3, 27.6.
HRMS (EI) calculated for [C17H17NO4]+ requires m/z 299.1152, found m/z 299.1153.
2-Phenylcyclobutane-1-carbonitrile (16). The title compound was synthesized according to the General Procedure A using styrene (41.6 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol %), and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (5:1 v/v) as the eluent to give 41.5 mg (0.264 mmol, 66% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.39-7.31 (m, 2H), 7.30-7.19 (m, 3H), 3.96-3.78 (m, 1H), 3.13-3.01 (m, 1H), 2.45-2.21 (m, 4H).
13C NMR (CDCl3, 100 MHz): δ 141.2, 128.7, 127.2, 126.0, 121.3, 45.0, 29.2, 26.5, 23.1.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.43-7.34 (m, 2H), 7.33-7.24 (m, 3H), 3.95-3.84 (m, 1H), 3.56-3.46 (m, 1H), 2.75-2.60 (m, 1H), 2.55-2.35 (m, 2H), 2.34-2.25 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 139.2, 128.6, 127.4, 127.1, 120.8, 41.7, 30.7, 25.7, 23.2.
HRMS (EI) calculated for [CiiHiiN]+ requires m/z 157.0886, found m/z 157.0870.
2-(4-Methoxyphenyl)cyclobutane-1-carbonitrile (17). The title compound was synthesized according to the General Procedure A using 1-methoxy-4-vinylbenzene (53.7 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol %), and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (5:1 v/v) as the eluent to give 48.7 mg (0.260 mmol, 65% yield, 1.2:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.16 (d, J=8.6 Hz, 2H), 6.88 (d, J=8.6 Hz, 2H), 3.85-3.73 (m, 4H), 3.07-2.94 (m, 1H), 2.40-2.17 (m, 4H).
13C NMR (CDCl3, 100 MHz): δ 158.7, 133.3, 127.2, 121.4, 114.0, 55.3, 44.6, 29.6, 26.8, 23.0.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.23 (d, J=8.6 Hz, 2H), 6.91 (d, J=8.6 Hz, 2H), 3.88-3.77 (m, 4H), 3.52-3.41 (m, 1H), 2.69-2.57 (m, 1H), 2.50-2.32 (m, 2H), 2.30-2.22 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 158.8, 131.4, 128.3, 121.0, 113.9, 55.2, 41.2, 30.9, 26.0, 23.0.
HRMS (EI) calculated for [C12H13NO]+ requires m/z 187.0992, found m/z 187.0980.
2-(p-Tolyl)cyclobutane-1-carbonitrile (18). The title compound was synthesized according to the General Procedure A using 1-methyl-4-vinylbenzene (47.3 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol %), and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (5:1 v/v) as the eluent to give 41.0 mg (0.240 mmol, 60% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.19-7.10 (m, 4H), 3.89-3.75 (m, 1H), 3.09-2.98 (m, 1H), 2.42-2.22 (m, 7H).
13C NMR (CDCl3, 100 MHz): δ 138.3, 136.9, 129.3, 125.9, 121.4, 44.8, 29.4, 26.6, 23.1, 21.0.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.18 (s, 4H), 3.93-3.78 (m, 1H), 3.55-3.41 (m, 1H), 2.71-2.59 (m, 1H), 2.52-2.24 (m, 6H).
13C NMR (CDCl3, 100 MHz): δ 137.0, 136.2, 129.2, 127.0, 120.9, 41.5, 30.8, 25.8, 23.1, 21.1.
HRMS (EI) calculated for [C12H13N]+ requires m/z 171.1043, found m/z 171.1039.
2-([1,1′-Biphenyl]-4-yl)cyclobutane-1-carbonitrile (19). The title compound was synthesized according to the General Procedure A using 4-vinyl-1,1′-biphenyl (36.1 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1 v/v) as the eluent to give 24.7 mg (0.106 mmol, 53% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.60-7.54 (m, 4H), 7.48-7.40 (m, 2H), 7.38-7.28 (m, 3H), 3.98-3.82 (m, 1H), 3.18-3.03 (m, 1H), 2.49-2.22 (m, 4H).
13C NMR (CDCl3, 100 MHz): δ 140.6, 140.2, 128.8, 127.39, 127.36, 127.0, 126.5, 121.3, 44.8, 29.3, 26.6, 23.2.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.65-7.55 (m, 4H), 7.48-7.40 (m, 2H), 7.39-7.29 (m, 3H), 4.03-3.84 (m, 1H), 3.61-3.38 (m, 1H), 2.79-2.62 (m, 1H), 2.56-2.37 (m, 2H), 2.36-2.26 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 140.7, 140.2, 138.3, 128.7, 127.6, 127.3, 127.2, 127.1, 120.8, 41.5, 30.7, 25.8, 23.2.
HRMS (EI) calculated for [C17H15N]+ requires m/z 233.1199, found m/z 233.1206.
Methyl 4-(2-cyanocyclobutyl)benzoate (20). The title compound was synthesized according to the General Procedure A using methyl 4-vinylbenzoate (32.4 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (5:1 v/v) as the eluent to give 20.7 mg (0.096 mmol, 48% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 8.02 (d, J=8.4 Hz, 2H), 7.30 (d, J=8.4 Hz, 2H), 3.98-3.86 (m, 4H), 3.16-3.06 (m, 1H), 2.48-2.22 (m, 4H).
13C NMR (CDCl3, 100 MHz): δ 166.7, 146.2, 130.0, 129.1, 126.0, 121.0, 52.2, 44.7, 29.0, 26.3, 23.2.
Minor: 1H NMR (CDCl3, 400 MHz): δ 8.06 (d, J=8.4 Hz, 2H), 7.35 (d, J=8.4 Hz, 2H), 4.01-3.88 (m, 4H), 3.60-3.51 (m, 1H), 2.75-2.64 (m, 1H), 2.58-2.40 (m, 2H), 2.36-2.27 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 166.8, 144.4, 129.9, 129.2, 127.1, 120.4, 52.1, 41.5, 30.5, 25.5, 23.2.
HRMS (EI) calculated for [C13H13NO2]+ requires m/z 215.0941, found m/z 215.0938.
2-(4-(Trifluoromethyl)phenyl)cyclobutane-1-carbonitrile (21). The title compound was synthesized according to the General Procedure A using 1-(trifluoromethyl)-4-vinylbenzene (68.9 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol %), and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (5:1 v/v) as the eluent to give 52.2 mg (0.232 mmol, 58% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.61 (d, J=8.0 Hz, 2H), 7.35 (d, J=8.0 Hz, 2H), 3.99-3.89 (m, 1H), 3.14-3.04 (m, 1H), 2.49-2.22 (m, 4H).
19F NMR (CDCl3, 376 MHz): δ −62.5.
13C NMR (CDCl3, 100 MHz): δ 145.1, 129.6 (q, J=33.0 Hz), 126.4, 125.7 (q, J=3.8 Hz), 124.0 (q, J=270.0 Hz), 120.8, 44.5, 29.0, 26.3, 23.2.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.64 (d, J=8.0 Hz, 2H), 7.40 (d, J=8.0 Hz, 2H), 4.01-3.90 (m, 1H), 3.61-3.51 (m, 1H), 2.75-2.63 (m, 1H), 2.58-2.42 (m, 2H), 2.36-2.28 (m, 1H).
19F NMR (CDCl3, 376 MHz): δ −62.5.
13C NMR (CDCl3, 100 MHz): δ 143.2, 129.6 (q, J=32.4 Hz), 127.5, 125.6 (q, J=3.8 Hz), 124.1 (q, J=270.0 Hz), 120.4, 41.3, 30.5, 25.6, 23.2.
HRMS (EI) calculated for [C12H10F3N]+ requires m/z 225.0760, found m/z 225.0762.
2-(4-Chlorophenyl)cyclobutane-1-carbonitrile (22). The title compound was synthesized according to the General Procedure A using 1-chloro-4-vinylbenzene (55.4 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol %), and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (5:1 v/v) as the eluent to give 49.7 mg (0.260 mmol, 65% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.32 (d, J=8.4 Hz, 2H), 7.16 (d, J=8.4 Hz, 2H), 3.90-3.76 (m, 1H), 3.08-2.97 (m, 1H), 2.44-2.15 (m, 4H).
13C NMR (CDCl3, 100 MHz): δ 139.6, 133.0, 128.8, 127.4, 121.0, 44.4, 29.2, 26.5, 23.1.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.35 (d, J=8.4 Hz, 2H), 7.22 (d, J=8.4 Hz, 2H), 3.92-3.80 (m, 1H), 3.56-3.44 (m, 1H), 2.70-2.58 (m, 1H), 2.54-2.36 (m, 2H), 2.33-2.24 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 137.7, 133.2, 128.7, 128.5, 120.6, 41.1, 30.6, 25.7, 23.0.
HRMS (EI) calculated for [C11H10ClN]+ requires m/z 191.0496, found m/z 191.0501.
2-(Naphthalen-1-yl)cyclobutane-1-carbonitrile (23). The title compound was synthesized according to the General Procedure A using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1 v/v) as the eluent to give 28.1 mg (0.136 mmol, 68% yield, 1.6:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.01 (d, J=8.8 Hz, 0.62H), 7.91-7.85 (m, 1H), 7.85-7.74 (m, 1.38H), 7.59-7.41 (m, 3.38H), 7.35 (d, J=7.2 Hz, 0.62H), 4.67-4.48 (m, 1H), 3.84-3.70 (m, 0.38H), 3.38-3.27 (m, 0.62H), 3.11-2.93 (m, 0.38H), 2.66-2.26 (m, 3.62H).
13C NMR (CDCl3, 100 MHz): δ 136.8, 134.5, 133.8, 133.7, 131.02, 130.96, 129.1, 128.8, 128.1, 127.8, 126.4, 126.3, 126.0, 125.7, 125.34, 125.26, 124.4, 123.5, 122.6, 122.5, 121.4, 120.5, 42.5, 39.3, 31.9, 27.6, 27.2, 24.2, 23.4, 23.3.
HRMS (EI) calculated for [C15H13N]+ requires m/z 207.1043, found m/z 207.1046.
2-(4-Fluoronaphthalen-1-yl)cyclobutane-1-carbonitrile (24). The title compound was synthesized according to the General Procedure A using 1-fluoro-4-vinylnaphthalene (34.5 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (12:1 v/v) as the eluent to give 33.7 mg (0.150 mmol, 75% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 8.20-8.11 (m, 1H), 8.06-7.96 (m, 1H), 7.69-7.54 (m, 2H), 7.30-7.24 (m, 1H), 7.18-7.06 (m, 1H), 4.57-4.39 (m, 1H), 3.35-3.16 (m, 1H), 2.67-2.27 (m, 4H).
19F NMR (376 MHz, CDCl3): δ −123.9.
13C NMR (CDCl3, 100 MHz): δ 158.2 (d, J=252.0 Hz), 132.7 (d, J=4.4 Hz), 132.2 (d, J=4.4 Hz), 127.4, 126.3 (d, J=1.9 Hz), 124.0 (d, J=16.3 Hz), 123.6 (d, J=2.8 Hz), 122.4 (d, J=8.7 Hz), 121.32 (d, J=4.8 Hz), 121.31, 108.6 (d, J=20.0 Hz), 42.1, 27.9, 27.1, 23.4.
Minor: 1H NMR (CDCl3, 400 MHz): δ 8.21-8.13 (m, 1H), 7.83-7.75 (m, 1H), 7.63-7.53 (m, 2H), 7.45-7.37 (m, 1H), 7.22-7.12 (m, 1H), 4.56-4.38 (m, 1H), 3.85-3.62 (m, 1H), 3.10-2.89 (m, 1H), 2.68-2.53 (m, 1H), 2.51-2.39 (m, 1H), 2.37-2.22 (m, 1H).
19F NMR (376 MHz, CDCl3): δ −123.59.
13C NMR (CDCl3, 100 MHz): δ 158.4 (d, J=252.3 Hz), 132.3 (d, J=4.4 Hz), 130.4 (d, J=4.3 Hz), 127.3, 126.1 (d, J=1.9 Hz), 124.4 (d, J=8.7 Hz), 124.0 (d, J=16.4 Hz), 122.7 (d, J=2.9 Hz), 121.7 (d, J=5.8 Hz), 120.4, 108.8 (d, J=20.1 Hz), 39.0, 31.9, 24.3, 23.3.
HRMS (EI) calculated for [C15H12FN]+ requires m/z 225.0948, found m/z 225.0958.
2-(Phenanthren-9-yl)cyclobutane-1-carbonitrile (25). The title compound was synthesized according to the General Procedure A using 9-vinylphenanthrene (40.9 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1 v/v) as the eluent to give 38.6 mg (0.150 mmol, 75% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.78-8.70 (m, 1H), 8.65 (d, J=8.1 Hz, 1H), 8.07-8.00 (m, 0.56H), 7.95-7.85 (m, 1H), 7.83-7.77 (m, 0.44H), 7.72-7.55 (m, 5H), 4.59-4.43 (m, 1H), 3.86-3.76 (m, 0.44H), 3.45-3.36 (m, 0.56H), 3.24-2.99 (m, 0.56H), 2.72-2.30 (m, 3.44H).
13C NMR (CDCl3, 100 MHz): δ 135.2, 132.8, 131.4, 131.2, 130.8, 130.7, 130.13, 130.12, 130.0, 129.8, 128.8, 128.5, 126.93, 126.92, 126.81, 126.79, 126.76, 126.7, 126.5, 125.7, 124.3, 123.6, 123.5, 123.34, 123.26, 122.5, 121.5, 120.4, 42.7, 39.7, 31.9, 27.3, 27.2, 24.0, 23.44, 23.36.
HRMS (EI) calculated for [C19H15N]+ requires m/z 257.1199, found m/z 257.1207.
2-(Quinolin-8-yl)cyclobutane-1-carbonitrile (26). The title compound was synthesized according to the General Procedure A using 8-vinylquinoline (31.0 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (6:1 v/v) as the eluent to give 26.2 mg (0.126 mmol, 63% yield, 1.7:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.95 (dd, J=4.2, 1.8 Hz, 0.62H), 8.88 (dd, J=4.2, 1.8 Hz, 0.38H), 8.19-8.12 (m, 1H), 7.79-7.71 (m, 1H), 7.70-7.65 (m, 0.38H), 7.61-7.48 (m, 1.62H), 7.45-7.39 (m, 1H), 4.98-4.76 (m, 1H), 3.98-3.85 (m, 0.38H), 3.54-3.40 (m, 0.62H), 2.97-2.86 (m, 0.38H), 2.68-2.21 (m, 3.62H).
13C NMR (CDCl3, 100 MHz): δ 149.4, 146.4, 146.2, 139.5, 137.7, 136.4, 136.1, 128.3, 128.2, 127.4, 127.3, 127.1, 126.21, 126.19, 126.0, 122.1, 121.6, 121.3, 121.2, 42.1, 38.3, 32.3, 28.5, 26.9, 24.2, 23.8, 23.4.
HRMS (EI) calculated for [C14H12N21 requires m/z 208.0995, found m/z 208.1004.
2-(Isoquinolin-4-yl)cyclobutane-1-carbonitrile (27). The title compound was synthesized according to the General Procedure A using 4-vinylisoquinoline (31.1 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (3:1 v/v) as the eluent to give 31.2 mg (0.150 mmol, 75% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.24 (s, 0.38H), 9.20 (s, 0.62H), 8.53 (s, 0.38H), 8.44 (s, 0.62H), 8.11-7.98 (m, 1.62H), 7.84-7.73 (m, 1.38H), 7.72-7.60 (m, 1H), 4.59-4.39 (m, 1H), 3.90-3.70 (m, 0.38H), 3.39-3.26 (m, 0.62H), 3.16-3.02 (m, 0.38H), 2.71-2.34 (m, 3.62H).
13C NMR (CDCl3, 100 MHz): δ 152.7, 152.4, 141.2, 139.7, 133.8, 133.7, 131.0, 130.9, 129.9, 128.8, 128.5, 128.2, 128.1, 127.5, 127.3, 122.7, 121.9, 121.1, 120.0, 40.5, 37.5, 31.5, 28.1, 26.2, 23.9, 23.72, 23.66.
HRMS (EI) calculated for [C14H12N2]+ requires m/z 208.0995, found m/z 208.1001.
2-(Isoquinolin-5-yl)cyclobutane-1-carbonitrile (28). The title compound was synthesized according to the General Procedure A using 5-vinylisoquinoline (31.1 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (3:1 v/v) as the eluent to give 20.1 mg (0.096 mmol, 48% yield, 1.7:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.31 (brs, 1H), 8.62 (brs, 1H), 8.02-7.87 (m, 1H), 7.85-7.79 (m, 0.60H), 7.76-7.72 (m, 0.40H), 7.71-7.56 (m, 2H), 4.66-4.26 (m, 1H), 3.85-3.68 (m, 0.40H), 3.31 (q, J=9.0 Hz, 0.60H), 3.14-2.93 (m, 0.40H), 2.67-2.33 (m, 3.60H).
13C NMR (CDCl3, 100 MHz): δ 153.3, 153.1, 143.5, 143.4, 136.2, 134.0, 133.82, 133.78, 129.6, 128.7, 128.1, 127.6, 127.3, 127.0, 126.83, 126.79, 125.9, 123.7, 121.1, 120.1, 41.8, 38.5, 31.6, 27.8, 26.9, 24.2, 23.4, 23.3.
HRMS (EI) calculated for [C14H12N21 requires m/z 208.0995, found m/z 208.1003.
2-Methyl-2-(naphthalen-2-yl)cyclobutane-1-carbonitrile (29). The title compound was synthesized according to the General Procedure A using 2-(prop-1-en-2-yl)naphthalene (68.0 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol %), and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (5:1 v/v) as the eluent to give 49.6 mg (0.224 mmol, 56% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.86-7.78 (m, 3H), 7.56-7.43 (m, 3H), 7.32-7.26 (m, 1H), 3.43 (t, J=9.2 Hz, 1H), 2.63-2.44 (m, 2H), 2.41-2.30 (m, 1H), 2.25-2.16 (m, 1H), 1.73 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 146.3, 133.2, 132.0, 128.6, 127.7, 127.6, 126.4, 125.8, 122.7, 122.3, 120.3, 45.8, 32.3, 32.0, 27.0, 21.3.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.87 (d, J=8.6 Hz, 1H), 7.85-7.80 (m, 2H), 7.65 (d, J=2.0 Hz, 1H), 7.51-7.43 (m, 2H), 7.35 (dd, J=8.6, 2.0 Hz, 1H), 3.28-3.19 (m, 1H), 3.07-2.96 (m, 1H), 2.68-2.56 (m, 1H), 2.32-2.16 (m, 2H), 1.65 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 142.6, 133.3, 132.2, 128.4, 127.9, 127.7, 126.2, 125.8, 123.8, 123.7, 121.1, 46.6, 34.8, 31.2, 30.6, 21.1.
HRMS (EI) calculated for [C16H15N]+ requires m/z 221.1199, found m/z 221.1193.
3-Methyl-2-(naphthalen-2-yl)cyclobutane-1-carbonitrile (30). The title compound was synthesized according to the General Procedure A using 2-(prop-1-en-1-yl)naphthalene (E:Z=4:1) (34.0 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (10:1 v/v) as the eluent to give 39.2 mg (0.178 mmol, 89% yield, 1.1:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.86-7.78 (m, 3H), 7.64 (s, 1H), 7.52-7.44 (m, 2H), 7.36 (dd, J=8.4, 1.8 Hz, 1H), 3.48 (t, J=9.4 Hz, 1H), 3.08-2.96 (m, 1H), 2.69-2.50 (m, 2H), 2.02 (q, J=10.0 Hz, 1H), 1.27 (d, J=6.4 Hz, 3H).
13C NMR (CDCl3, 100 MHz): δ 137.7, 133.3, 132.6, 128.6, 127.69, 127.67, 126.4, 125.9, 124.8, 124.4, 121.4, 53.1, 36.1, 31.3, 25.9, 20.4.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.89-7.80 (m, 3H), 7.75-7.71 (m, 1H), 7.52-7.43 (m, 2H), 7.40 (dd, J=8.4, 1.8 Hz, 1H), 3.62-3.39 (m, 2H), 3.31-3.14 (m, 1H), 2.50-2.41 (m, 1H), 2.14-2.03 (m, 1H), 1.25 (d, J=6.4 Hz, 3H).
13C NMR (CDCl3, 100 MHz): δ 135.9, 133.3, 132.8, 128.4, 127.9, 127.7, 126.2, 126.0, 125.9, 125.4, 121.2, 49.6, 34.8, 30.8, 28.3, 20.3.
HRMS (EI) calculated for [C16H15N]+ requires m/z 221.1199, found m/z 221.1187.
3,3-Dimethyl-2-(naphthalen-2-yl)cyclobutane-1-carbonitrile (31). The title compound was synthesized according to the General Procedure A using 2-(2-methylprop-1-en-1-yl)naphthalene (36.5 mg, 0.2 mmol), acrylonitrile (66 μL, 1.0 mmol), and UiO-69-phen(binap)Cu (5.9 mg, 1 μmol based on Cu, 0.5 mol %). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (10:1 v/v) as the eluent to give 45.1 mg (0.192 mmol, 96% yield, 1.2:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.92-7.71 (m, 3.50H), 7.58-7.37 (m, 3H), 7.19 (d, J=8.4 Hz, 0.50H), 3.81-3.38 (m, 2H), 2.42-2.03 (m, 2H), 1.41-1.29 (m, 3H), 1.10 (s, 1.50H), 0.76 (s, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 135.0, 134.9, 133.24, 133.19, 132.43, 132.38, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, 126.8, 126.3, 126.14, 126.09, 125.80, 125.79, 125.1, 124.9, 122.0, 121.8, 54.1, 51.3, 40.6, 39.7, 37.5, 36.9, 30.8, 30.4, 24.2, 22.9, 22.2, 20.5.
HRMS (EI) calculated for [C17H17N]+ requires m/z 235.1356, found m/z 235.1356.
1-(Naphthalen-2-yl)spiro[3.3]heptane-2-carbonitrile (32). The title compound was synthesized according to the General Procedure A using 2-(cyclobutylidenemethyl)naphthalene (38.9 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (10:1 v/v) as the eluent to give 46.9 mg (0.190 mmol, 95% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.90-7.80 (m, 3H), 7.81-7.73 (m, 0.44H), 7.59-7.54 (m, 0.56H), 7.53-7.43 (m, 2.44H), 7.29 (dd, J=8.5, 1.9 Hz, 0.56H), 3.79-3.64 (m, 1H), 3.59-3.45 (m, 0.44H), 3.34-3.21 (m, 0.56H), 2.75-2.63 (m, 0.44H), 2.61-2.54 (m, 0.44H), 2.51-2.36 (m, 1H), 2.23-1.63 (m, 5.56H), 1.57-1.49 (m, 0.56H).
13C NMR (CDCl3, 100 MHz): δ 135.0, 134.9, 133.31, 133.28, 132.58, 132.57, 128.3, 128.1, 127.9, 127.7, 127.63, 127.59, 127.4, 126.3, 126.2, 126.1, 125.9, 125.8, 125.7, 125.3, 121.4, 121.0, 53.7, 52.2, 47.2, 46.9, 38.3, 37.1, 35.4, 33.3, 30.7, 28.8, 24.3, 21.7, 15.89, 15.86.
HRMS (EI) calculated for [C18H17N]+ requires m/z 247.1356, found m/z 247.1356.
1-(Naphthalen-2-yl)spiro[3.4]octane-2-carbonitrile (33). The title compound was synthesized according to the General Procedure A using 2-(cyclopentylidenemethyl)naphthalene (41.6 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (10:1 v/v) as the eluent to give 26.8 mg (0.102 mmol, 51% yield, 1.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.89-7.77 (m, 3.50H), 7.58-7.42 (m, 3H), 7.26-7.21 (m, 0.50H), 3.96 (d, J=10.2 Hz, 0.50H), 3.76 (d, J=9.2 Hz, 0.50H), 3.67-3.55 (m, 0.50H), 3.42 (q, J=9.2 Hz, 0.50H), 2.54-2.20 (m, 2H), 1.95-1.76 (m, 2H), 1.65-1.26 (m, 6H).
13C NMR (CDCl3, 100 MHz): δ 135.1, 135.0, 133.3, 133.2, 132.52, 132.50, 128.1, 127.90, 127.87, 127.7, 127.61, 127.56, 127.5, 126.5, 126.3, 126.1, 125.9, 125.8, 125.5, 125.4, 121.7, 121.4, 52.9, 51.4, 51.1, 51.0, 40.9, 39.9, 38.0, 37.6, 34.3, 32.6, 24.0, 23.7, 23.6, 23.5, 23.4, 21.4.
HRMS (EI) calculated for [C19H19N]+ requires m/z 261.1512, found m/z 261.1515.
1-(Naphthalen-2-yl)spiro[3.5]nonane-2-carbonitrile (34). The title compound was synthesized according to the General Procedure A using 2-(cyclohexylidenemethyl)naphthalene (44.5 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (10:1 v/v) as the eluent to give 28.2 mg (0.102 mmol, 51% yield, 1.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.92-7.73 (m, 3.50H), 7.58-7.41 (m, 3H), 7.26-7.19 (m, 0.50H), 3.70 (d, J=10.2 Hz, 0.50H), 3.67-3.55 (m, 1H), 3.47 (q, J=9.2 Hz, 0.50H), 2.44-2.08 (m, 2H), 1.88-0.76 (m, 10H).
13C NMR (CDCl3, 100 MHz): δ 134.4, 134.24, 133.20, 133.1, 132.47, 132.45, 128.0, 127.9, 127.7, 127.6, 127.5, 127.0, 126.3, 126.1, 125.82, 125.77, 125.3, 122.1, 121.7, 54.5, 51.9, 44.1, 40.5, 39.5, 35.3, 33.9, 33.2, 30.9, 25.6, 25.5, 22.93, 22.91, 22.8, 21.90, 21.86, 20.5.
HRMS (EI) calculated for [C20H21N]+ requires m/z 275.1669, found m/z 275.1671.
2-(2-([1,1′-Biphenyl]-4-yl)-1-methylcyclobutyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (35). The title compound was synthesized according to the General Procedure A using 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (168 mg, 1.0 mmol) and 4-vinyl-1,1′-biphenyl (36.1 mg, 0.2 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (30:1 v/v) as the eluent to give 31.3 mg (0.090 mmol, 45% yield, 3.4:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.59 (d, J=8.0 Hz, 2H), 7.53 (d, J=8.0 Hz, 2H), 7.46-7.37 (m, 2H), 7.34-7.28 (m, 1H), 7.26-7.19 (m, 2H), 3.87-3.75 (m, 1H), 2.69-2.57 (m, 1H), 2.36-2.19 (m, 2H), 1.55-1.46 (m, 1H), 1.30 (s, 12H), 0.89 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 141.6, 141.2, 138.3, 128.6, 127.9, 127.0, 126.9, 126.6, 83.2, 42.8, 27.1, 24.8, 24.7, 22.7, 17.5.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.55 (d, J=7.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 7.44-7.39 (m, 2H), 7.34-7.31 (m, 1H), 7.30-7.27 (m, 2H), 3.33-3.23 (m, 1H), 2.55-2.44 (m, 1H), 2.22-2.11 (m, 2H), 1.70-1.61 (m, 1H), 1.38 (s, 3H), 0.95 (s, 6H), 0.91 (s, 6H).
13C NMR (CDCl3, 100 MHz): δ 143.6, 141.5, 138.6, 128.7, 127.2, 127.0, 126.9, 126.6, 82.8, 50.4, 29.0, 26.2, 24.7, 24.6, 22.0.
HRMS (EI) calculated for [C23H29BO2]+ requires m/z 348.2255, found m/z 348.2250.
6-(2-Phenylcyclobutyl)quinoline (36). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (311 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (5:1 v/v) as the eluent to give 363 mg (1.40 mmol, 70% yield, 2.9:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.37-8.96 (m, 1H), 8.59-8.37 (m, 1H), 7.90 (d, J=8.4 Hz, 0.75H), 7.70-7.57 (m, 1.75H), 7.53-7.46 (m, 1H), 7.44 (s, 0.25H), 7.36-7.29 (m, 1.50H), 7.27-7.20 (m, 2.25H), 7.13-6.91 (m, 1.50H), 4.28-4.08 (m, 0.50H), 3.84-3.63 (m, 1.50H), 2.65-2.49 (m, 1H), 2.48-2.35 (m, 1.50H), 2.32-2.18 (m, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 149.7, 149.5, 147.3, 146.9, 144.2, 142.9, 141.0, 140.2, 135.7, 135.6, 130.7, 129.3, 129.1, 128.4, 128.3, 128.2, 127.80, 127.78, 126.6, 126.2, 125.7, 125.4, 124.4, 121.1, 120.8, 47.9, 47.8, 45.3, 45.1, 26.0, 25.9, 24.3, 24.2.
HRMS (EI) calculated for [C19H17N]+ requires m/z 259.1356, found m/z 259.1360.
6-(2-(4-Methoxyphenyl)cyclobutyl)quinoline (37). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (312 mg, 2.0 mmol) and 1-methoxy-4-vinylbenzene (1.3 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 440 mg (1.52 mmol, 76% yield, 3.2:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.86 (s, 1H), 8.15-7.75 (m, 2H), 7.66-7.28 (m, 2.52H), 7.25-7.11 (m, 2H), 6.92-6.81 (m, 2H), 6.57 (d, J=8.8 Hz, 0.48H), 4.25-4.02 (m, 0.48H), 3.83-3.55 (m, 4.52H), 2.62-2.47 (m, 0.96H), 2.45-2.31 (m, 1.52H), 2.28-2.13 (m, 1.52H).
13C NMR (CDCl3, 100 MHz): δ 158.1, 157.5, 142.9, 140.3, 136.3, 135.71, 135.65, 133.2, 130.8, 129.30, 129.26, 129.2, 129.1, 128.8, 127.6, 125.4, 124.4, 113.82, 113.77, 113.7, 113.2, 55.2, 55.0, 48.2, 47.5, 45.1, 44.6, 26.3, 25.6, 24.6, 24.1.
HRMS (EI) calculated for [C20H19NO]+ requires m/z 289.1461, found m/z 289.1462.
4-(2-(Quinolin-6-yl)cyclobutyl)phenyl acetate (38). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (313 mg, 2.0 mmol) and 4-vinylphenyl acetate (1.6 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 425 mg (1.34 mmol, 67% yield, 3.3:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.86 (dd, J=4.2, 1.6 Hz, 0.77H), 8.79 (dd, J=4.2, 1.6 Hz, 0.23H), 8.10 (dd, J=8.4, 1.0 Hz, 0.77H), 8.06-8.02 (m, 0.77H), 8.01-7.98 (m, 0.23H), 7.80 (d, J=8.4 Hz, 0.23H), 7.65-7.57 (m, 1.54H), 7.41-7.34 (m, 1H), 7.33-7.29 (m, 0.23H), 7.28-7.21 (m, 1.77H), 7.05-6.99 (m, 1.54H), 6.95 (d, J=8.4 Hz, 0.46H), 6.76 (d, J=8.4 Hz, 0.46H), 4.30-3.99 (m, 0.46H), 3.81-3.59 (m, 1.54H), 2.63-2.46 (m, 0.92H), 2.46-2.34 (m, 1.54H), 2.32-2.16 (m, 4.54H).
13C NMR (CDCl3, 100 MHz): δ 169.7, 169.4, 149.8, 149.6, 149.0, 148.6, 147.3, 146.9, 142.6, 141.8, 139.9, 138.7, 135.8, 135.7, 130.6, 129.4, 129.0, 128.7, 128.5, 128.2, 127.9, 127.5, 125.5, 124.4, 121.4, 121.2, 120.9, 120.8, 47.9, 47.3, 45.0, 44.7, 26.0, 25.9, 24.4, 24.2, 21.1, 21.0.
HRMS (EI) calculated for [C21H19NO2]+ requires m/z 317.1410, found m/z 317.1410.
6-(2-(p-Tolyl)cyclobutyl)quinoline (39). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (312 mg, 2.0 mmol) and 1-methyl-4-vinylbenzene (1.2 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 355 mg (1.30 mmol, 65% yield, 3.1:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.20 (s, 0.75H), 9.09 (s, 0.25H), 8.56-8.33 (m, 1H), 7.89 (d, J=8.4 Hz, 0.75H), 7.73-7.38 (m, 3H), 7.22-7.03 (m, 3.25H), 6.84 (s, 1H), 4.28-4.01 (m, 0.50H), 3.84-3.56 (m, 1.50H), 2.60-2.13 (m, 7H).
13C NMR (CDCl3, 100 MHz): δ 149.7, 149.5, 147.2, 146.9, 143.0, 141.2, 140.4, 138.0, 135.8, 135.78, 135.72, 135.1, 130.8, 129.3, 129.08, 129.07, 128.5, 128.3, 128.20, 128.19, 127.7, 126.5, 125.4, 124.3, 121.1, 120.8, 47.9, 47.7, 45.0, 44.9, 26.1, 25.7, 24.4, 24.2, 21.0, 20.8.
HRMS (EI) calculated for [C20H19N]+ requires m/z 273.1512, found m/z 273.1514.
6-(2-(4-Chlorophenyl)cyclobutyl)quinoline (40). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (311 mg, 2.0 mmol) and 1-chloro-4-vinylbenzene (1.4 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 305 mg (1.04 mmol, 52% yield, 2.9:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.21 (s, 0.75H), 9.10 (s, 0.25H), 8.57-8.39 (m, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.70-7.41 (m, 3H), 7.30-7.26 (m, 1H), 7.21-7.05 (m, 2H), 7.02-6.96 (m, 0.50H), 6.91-6.79 (m, 0.50H), 4.25-4.06 (m, 0.50H), 3.79-3.58 (m, 1.50H), 2.68-2.49 (m, 1H), 2.47-2.35 (m, 1.50H), 2.32-2.14 (m, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 152.1, 152.0, 146.6, 143.1, 143.0, 142.9, 142.4, 136.0, 135.6, 132.0, 129.12, 129.07, 128.5, 128.4, 128.0, 127.9, 127.8, 127.6, 126.97, 126.95, 126.8, 126.5, 124.1, 123.11, 123.06, 120.3, 48.3, 47.3, 45.3, 44.6, 26.0, 25.5, 24.4, 23.8.
HRMS (EI) calculated for [C19H16ClN]+ requires m/z 293.0966, found m/z 293.0969.
6-(2-(4-Fluorophenyl)cyclobutyl)quinoline (41). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (313 mg, 2.0 mmol) and 1-fluoro-4-vinylbenzene (1.2 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (4:1 v/v) as the eluent to give 372 mg (1.34 mmol, 67% yield, 2.8:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.86 (dd, J=4.2, 1.8 Hz, 0.74H), 8.80 (dd, J=4.2, 1.8 Hz, 0.26H), 8.13-8.03 (m, 1.48H), 8.02-7.97 (m, 0.26H), 7.80 (d, J=8.8 Hz, 0.26H), 7.62-7.56 (m, 1.48H), 7.42-7.35 (m, 1H), 7.34-7.29 (m, 0.26H), 7.24-7.18 (m, 1.74H), 7.03-6.95 (m, 1.48H), 6.92-6.87 (m, 0.52H), 6.75-6.67 (m, 0.52H), 4.22-4.04 (m, 0.52H), 3.77-3.56 (m, 1.48H), 2.62-2.47 (m, 1.04H), 2.46-2.35 (m, 1.48H), 2.30-2.13 (m, 1.48H).
19F NMR (CDCl3, 376 MHz): δ −116.9, −117.4.
13C NMR (CDCl3, 100 MHz): δ 161.4 (d, J=244.1 Hz), 161.0 (d, J=243.8 Hz), 149.8, 149.6, 147.3, 146.9, 142.5, 139.9, 139.8 (d, J=3.2 Hz), 136.7 (d, J=3.2 Hz), 135.8, 135.7, 130.6, 129.4, 129.1 (d, J=7.8 Hz), 129.0, 128.5, 128.2, 128.0 (d, J=7.8 Hz), 127.9, 125.5, 124.4, 121.2, 120.9, 115.1 (d, J=21.2 Hz), 114.6 (d, J=21.1 Hz), 48.2, 47.4, 45.0, 44.5, 26.1, 25.7, 24.4, 23.9.
HRMS (EI) calculated for [C19H16FN]+ requires m/z 277.1261, found m/z 277.1262.
6-(2-(4-(Trifluoromethyl)phenyl)cyclobutyl)quinoline (42). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (313 mg, 2.0 mmol) and 1-(trifluoromethyl)-4-vinylbenzene (1.7 g, mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (5:1 v/v) as the eluent to give 563 mg (1.72 mmol, 86% yield, 3.3:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.87 (dd, J=4.2, 1.6 Hz, 0.77H), 8.80 (dd, J=4.2, 1.6 Hz, 0.23H), 8.11 (dd, J=8.4, 1.6 Hz, 0.77H), 8.08-8.04 (m, 0.77H), 7.99 (dd, J=8.4, 1.6 Hz, 0.23H), 7.80 (d, J=8.7 Hz, 0.23H), 7.64-7.59 (m, 1.54H), 7.56 (d, J=8.2 Hz, 1.54H), 7.41-7.27 (m, 3.23H), 7.23 (dd, J=8.8, 2.0 Hz, 0.23H), 7.06 (d, J=8.4 Hz, 0.46H), 4.29-4.10 (m, 0.46H), 3.85-3.67 (m, 1.54H), 2.65-2.49 (m, 0.92H), 2.48-2.39 (m, 1.54H), 2.35-2.20 (m, 1.54H).
19F NMR (CDCl3, 376 MHz): δ −62.3, −62.4.
13C NMR (CDCl3, 100 MHz): δ 149.9, 149.7, 148.1, 147.2, 146.9, 145.3, 142.2, 139.5, 135.8, 135.7, 130.4, 129.5, 128.9, 128.67, 128.65, 128.5 (q, J=31.8 Hz), 128.2 (q, J=32.1 Hz), 128.0, 126.9, 125.6, 125.5, 125.3 (q, J=3.8 Hz), 124.7 (q, J=3.8 Hz), 124.5, 124.3 (q, J=270.2 Hz), 124.2 (q, J=270.2 Hz), 121.3, 121.0, 47.9, 47.6, 45.0, 25.9, 25.7, 24.24, 24.18.
HRMS (EI) calculated for [C20H16F3N]+ requires m/z 327.1229, found m/z 327.1231.
6-(2-(m-Tolyl)cyclobutyl)quinoline (43). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (313 mg, 2.0 mmol) and 1-methyl-3-vinylbenzene (1.2 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 421 mg (1.54 mmol, 77% yield, 3.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.85 (dd, J=4.4, 1.8 Hz, 0.75H), 8.78 (dd, J=4.4, 1.8 Hz, 0.25H), 8.12-8.07 (m, 0.75H), 8.06-7.98 (m, 1H), 7.79 (d, J=8.8 Hz, 0.25H), 7.64-7.56 (m, 1.50H), 7.41 (d, J=2.0 Hz, 0.25H), 7.36 (dd, J=8.4, 4.4 Hz, 0.75H), 7.30 (dd, J=8.4, 4.4 Hz, 0.25H), 7.24-7.17 (m, 1H), 7.09-7.01 (m, 2.25H), 6.93-6.88 (m, 0.25H), 6.79-6.71 (m, 0.75H), 4.24-4.02 (m, 0.50H), 3.85-3.57 (m, 1.50H), 2.61-2.47 (m, 1H), 2.44-2.35 (m, 1.50H), 2.33 (s, 2.25H), 2.27-2.18 (m, 1.50H), 2.10 (s, 0.75H).
13C NMR (CDCl3, 100 MHz): δ 149.6, 149.3, 147.2, 146.8, 144.1, 143.0, 140.9, 140.4, 138.0, 137.1, 135.80, 135.75, 130.8, 129.3, 129.1, 128.7, 128.3, 128.21, 128.19, 127.8, 127.6, 127.3, 127.0, 126.5, 125.4, 124.8, 124.4, 123.7, 121.1, 120.8, 47.9, 47.7, 45.2, 45.1, 26.1, 25.9, 24.3, 24.2, 21.5, 21.3.
HRMS (EI) calculated for [C20H19N]+ requires m/z 273.1512, found m/z 273.1514.
6-(2-(3-Fluorophenyl)cyclobutyl)quinoline (44). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (310 mg, 2.0 mmol) and 1-fluoro-3-vinylbenzene (1.2 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (4:1 v/v) as the eluent to give 316 mg (1.14 mmol, 57% yield, 3.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.86 (dd, J=4.4, 1.6 Hz, 0.75H), 8.79 (dd, J=4.4, 1.6 Hz, 0.25H), 8.10 (dd, J=8.4, 1.6 Hz, 0.75H), 8.07-8.02 (m, 0.75H), 8.00 (dd, J=8.4, 2.0 Hz, 0.25H), 7.80 (d, J=8.8 Hz, 0.25H), 7.65-7.58 (m, 1.50H), 7.41 (d, J=2.0 Hz, 0.25H), 7.37 (dd, J=8.4, 4.4 Hz, 0.75H), 7.31 (dd, J=8.4, 4.4 Hz, 0.25H), 7.28-7.26 (m, 0.25H), 7.26-7.21 (m, 0.75H), 7.03-6.87 (m, 2.50H), 6.74-6.59 (m, 0.75H), 4.27-4.03 (m, 0.50H), 3.80-3.60 (m, 1.50H), 2.66-2.49 (m, 1H), 2.46-2.35 (m, 1.50H), 2.31-2.14 (m, 1.50H).
19F NMR (CDCl3, 376 MHz): δ −113.3, −114.1.
13C NMR (CDCl3, 100 MHz): δ 163.0 (d, J=245.6 Hz), 162.6 (d, J=244.8 Hz), 149.8, 149.6, 147.3, 146.9, 146.8 (d, J=6.9 Hz), 143.9 (d, J=6.9 Hz), 142.4, 139.7, 135.8, 135.7, 130.5, 129.8 (d, J=8.3 Hz), 129.5, 129.1 (d, J=8.3 Hz), 128.9, 128.6, 128.2, 127.9, 125.4, 124.4, 123.6 (d, J=2.7 Hz), 122.3 (d, J=2.8 Hz), 121.2, 120.9, 114.5 (d, J=21.1 Hz), 113.4 (d, J=20.9 Hz), 113.1 (d, J=21.1 Hz), 112.6 (d, J=21.0 Hz), 47.8, 47.6 (d, J=1.7 Hz), 45.01, 44.96 (d, J=1.6 Hz), 25.9, 25.8, 24.13, 24.08.
HRMS (EI) calculated for [C19H16FN]+ requires m/z 277.1261, found m/z 277.1263.
6-(2-(o-Tolyl)cyclobutyl)quinoline (45). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (311 mg, 2.0 mmol) and 1-methyl-2-vinylbenzene (1.2 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (4:1 v/v) as the eluent to give 519 mg (1.90 mmol, 95% yield, 3.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.84 (dd, J=4.4, 1.6 Hz, 0.75H), 8.76 (dd, J=4.4, 1.6 Hz, 0.25H), 8.16-7.98 (m, 1.50H), 7.93 (dd, J=8.4, 1.8 Hz, 0.25H), 7.75 (d, J=8.8 Hz, 0.25H), 7.68-7.56 (m, 1.50H), 7.45-7.33 (m, 1.75H), 7.30-7.26 (m, 0.50H), 7.24-7.17 (m, 1H), 7.14-7.11 (m, 1.50H), 7.05-6.98 (m, 0.25H), 6.96-6.85 (m, 0.50H), 4.33-4.14 (m, 0.50H), 4.05-3.67 (m, 1.50H), 2.75-2.56 (m, 1H), 2.50-2.41 (m, 1.50H), 2.29-2.18 (m, 3H), 2.12-2.01 (m, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 149.7, 149.5, 147.2, 146.9, 143.0, 141.9, 140.4, 138.6, 136.2, 135.9, 135.74, 135.71, 130.6, 130.2, 130.1, 129.8, 129.3, 129.0, 128.3, 128.2, 126.3, 126.1, 126.0, 125.9, 125.62, 125.60, 125.4, 124.3, 121.1, 120.8, 45.5, 45.2, 42.4, 26.7, 26.1, 25.2, 23.1, 19.74, 19.71.
HRMS (EI) calculated for [C20H19N]+ requires m/z 273.1512, found m/z 273.1514.
6-(2-(2-Fluorophenyl)cyclobutyl)quinoline (46). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (311 mg, 2.0 mmol) and 1-fluoro-2-vinylbenzene (1.2 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (4:1 v/v) as the eluent to give 360 mg (1.30 mmol, 65% yield, 2.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.85 (dd, J=4.4, 1.6 Hz, 0.71H), 8.77 (dd, J=4.4, 1.6 Hz, 0.29H), 8.09 (d, J=8.0 Hz, 0.71H), 8.04 (d, J=9.2 Hz, 0.71H), 7.99 (d, J=8.0 Hz, 0.29H), 7.78 (d, J=8.8 Hz, 0.29H), 7.65-7.58 (m, 1.42H), 7.45 (d, J=2.0 Hz, 0.29H), 7.41-7.28 (m, 2H), 7.21-7.17 (m, 0.71H), 7.15-7.09 (m, 0.71H), 7.07-7.05 (m, 0.29H), 7.01-6.94 (m, 0.71H), 6.94-6.88 (m, 0.29H), 6.88-6.78 (m, 0.29H), 6.76-6.66 (m, 0.29H), 4.44-4.17 (m, 0.58H), 4.08-3.77 (m, 1.42H), 2.71-2.34 (m, 2.58H), 2.32-2.10 (m, 1.42H).
19F NMR (CDCl3, 376 MHz): δ −116.2, −117.1.
13C NMR (CDCl3, 100 MHz): δ 160.8 (d, J=245.3 Hz), 160.6 (d, J=244.2 Hz), 149.8, 149.5, 147.3, 146.9, 142.6, 140.0, 135.8, 135.7, 130.8, 130.6, 130.4, 129.3, 129.0, 128.4, 128.21, 128.19, 128.1 (d, J=5.0 Hz), 128.0 (d, J=5.0 Hz), 127.8 (d, J=8.2 Hz), 127.5 (d, J=8.4 Hz), 125.3, 124.3, 124.1 (d, J=3.6 Hz), 123.4 (d, J=3.4 Hz), 121.1, 120.8, 115.3 (d, J=22.3 Hz), 114.5 (d, J=22.2 Hz), 46.3, 44.9, 41.2 (d, J=0.9 Hz), 38.5 (d, J=1.7 Hz), 26.6, 25.9 (d, J=1.9 Hz), 24.1, 22.7.
HRMS (EI) calculated for [C19H16FN]+ requires m/z 277.1261, found m/z 277.1260.
6-(2-(Pyridin-2-yl)cyclobutyl)quinoline (47). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (312 mg, 2.0 mmol) and 2-vinylpyridine (1.1 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 427 mg (1.64 mmol, 82% yield, 2.6:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.85 (dd, J=4.4, 1.6 Hz, 0.72H), 8.77 (dd, J=4.4, 1.6 Hz, 0.28H), 8.67-8.60 (m, 0.72H), 8.40-8.33 (m, 0.28H), 8.09 (d, J=8.2 Hz, 0.72H), 8.02 (d, J=8.8 Hz, 0.72H), 8.00-7.96 (m, 0.28H), 7.75 (d, J=8.8 Hz, 0.28H), 7.66-7.55 (m, 2H), 7.43 (d, J=2.0 Hz, 0.28H), 7.36 (dd, J=8.4, 4.4 Hz, 0.72H), 7.33-7.20 (m, 1H), 7.18-7.10 (m, 1.44H), 6.90-6.78 (m, 0.56H), 4.36-4.18 (m, 0.56H), 4.14-4.01 (m, 0.72H), 3.84-3.73 (m, 0.72H), 2.79-2.24 (m, 4H).
13C NMR (CDCl3, 100 MHz): δ 162.5, 160.7, 149.7, 149.6, 149.5, 148.7, 147.2, 146.8, 142.9, 140.1, 136.3, 135.74, 135.69, 135.5, 130.4, 129.3, 129.1, 128.3, 128.2, 127.8, 125.5, 124.3, 122.8, 121.8, 121.5, 121.1, 120.81, 120.78, 49.7, 47.1, 46.0, 44.7, 25.5, 24.9, 24.3, 22.6.
HRMS (EI) calculated for [C18H16N21 requires m/z 260.1308, found m/z 260.1309.
6-(2-(1-Methyl-1H-indol-5-yl)cyclobutyl)quinoline (48). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (311 mg, 2.0 mmol) and 1-methyl-5-vinyl-1H-indole (1.6 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (4:1 v/v) as the eluent to give 524 mg (1.68 mmol, 84% yield, 3.6:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.83 (dd, J=4.4, 1.6 Hz, 0.78H), 8.73 (dd, J=4.4, 1.6 Hz, 0.22H), 8.07 (d, J=8.4 Hz, 0.78H), 8.01 (d, J=9.2 Hz, 0.78H), 7.96 (d, J=8.4 Hz, 0.22H), 7.71 (d, J=8.8 Hz, 0.22H), 7.65-7.59 (m, 1.56H), 7.53 (s, 0.78H), 7.46 (d, J=2.0 Hz, 0.22H), 7.37-7.31 (m, 1H), 7.28-7.23 (m, 1.22H), 7.14 (dd, J=8.4, 1.7 Hz, 0.78H), 7.02 (d, J=3.1 Hz, 0.78H), 6.91 (d, J=8.4 Hz, 0.22H), 6.88 (d, J=3.2 Hz, 0.22H), 6.73 (dd, J=8.4, 1.6 Hz, 0.22H), 6.43 (d, J=3.2 Hz, 0.78H), 6.28 (d, J=3.2 Hz, 0.22H), 4.31-4.17 (m, 0.44H), 3.86-3.70 (m, 3.90H), 3.61 (s, 0.66H), 2.64-2.52 (m, 0.88H), 2.49-2.36 (m, 1.56H), 2.34-2.18 (m, 1.56H).
13C NMR (CDCl3, 100 MHz): δ 149.6, 149.2, 147.2, 146.8, 143.4, 140.9, 135.8, 135.7, 135.6, 135.2, 131.9, 131.0, 129.3, 129.2, 129.1, 128.52, 128.48, 128.21, 128.16, 128.1, 127.9, 125.3, 124.3, 122.2, 121.0, 120.8, 120.6, 119.4, 118.3, 109.1, 108.5, 100.6, 100.4, 48.5, 48.3, 45.4, 45.3, 32.8, 32.7, 26.8, 25.6, 25.0, 24.4.
HRMS (EI) calculated for [C22H20N2]+ requires m/z 312.1621, found m/z 312.1623.
6-(2-(Benzofuran-5-yl)cyclobutyl)quinoline (49). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (312 mg, 2.0 mmol) and 5-vinylbenzofuran (1.4 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (5:1 v/v) as the eluent to give 479 mg (1.60 mmol, 80% yield, 3.8:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.86 (s, 0.79H), 8.75 (s, 0.21H), 8.09 (d, J=8.4 Hz, 0.79H), 8.04 (d, J=9.2 Hz, 0.79H), 7.96 (dd, J=8.4, 1.6 Hz, 0.21H), 7.73 (d, J=8.8 Hz, 0.21H), 7.67-7.56 (m, 2.21H), 7.51-7.40 (m, 2H), 7.36 (dd, J=8.4, 4.4 Hz, 0.79H), 7.30-7.22 (m, 0.79H), 7.19 (dd, J=8.4, 1.6 Hz, 0.79H), 7.12 (d, J=8.4 Hz, 0.21H), 6.84 (dd, J=8.4, 1.6 Hz, 0.21H), 6.72 (d, J=2.2 Hz, 0.79H), 6.55 (d, J=2.2 Hz, 0.21H), 4.27-4.13 (m, 0.42H), 3.89-3.66 (m, 1.58H), 2.63-2.53 (m, 0.84H), 2.48-2.38 (m, 1.58H), 2.32-2.21 (m, 1.58H).
13C NMR (CDCl3, 100 MHz): δ 153.8, 153.3, 149.7, 149.4, 147.3, 146.8, 145.2, 144.7, 142.9, 140.3, 138.8, 135.8, 135.65, 135.63, 130.7, 129.3, 129.1, 128.3, 128.2, 127.8, 127.5, 127.0, 125.4, 124.5, 124.4, 123.2, 121.1, 120.8, 119.8, 118.7, 111.1, 110.5, 106.5, 106.4, 48.4, 48.0, 45.23, 45.17, 26.5, 25.8, 24.8, 24.2.
HRMS (EI) calculated for [C21H17NO]+ requires m/z 299.1305, found m/z 299.1307.
6-(2-(Benzo[b]thiophen-5-yl)cyclobutyl)quinoline (50). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (310 mg, 2.0 mmol) and 5-vinylbenzofuran (1.6 g, 2.0 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (4:1 v/v) as the eluent to give 536 mg (1.70 mmol, 85% yield, 3.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.85 (dd, J=4.4, 1.6 Hz, 0.75H), 8.74 (dd, J=4.4, 1.6 Hz, 0.25H), 8.10-8.01 (m, 1.50H), 7.94 (dd, J=8.4, 1.6 Hz, 0.25H), 7.80 (d, J=8.4 Hz, 0.75H), 7.73 (d, J=8.8 Hz, 0.25H), 7.70 (s, 0.75H), 7.64-7.59 (m, 1.50H), 7.50-7.45 (m, 0.50H), 7.44-7.39 (m, 1H), 7.35 (dd, J=8.4, 4.4 Hz, 0.75H), 7.29-7.23 (m, 2.25H), 7.12 (d, J=5.4 Hz, 0.25H), 6.87 (dd, J=8.4, 1.6 Hz, 0.25H), 4.28-4.17 (m, 0.50H), 3.87-3.71 (m, 1.50H), 2.66-2.52 (m, 1H), 2.50-2.37 (m, 1.50H), 2.33-2.20 (m, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 149.7, 149.4, 147.2, 146.8, 142.8, 140.4, 140.2, 139.8, 139.4, 137.7, 137.4, 137.2, 135.8, 135.6, 130.7, 129.3, 129.1, 128.4, 128.2, 127.8, 126.7, 126.1, 125.4, 124.8, 124.4, 123.7, 123.6, 123.5, 122.4, 122.2, 121.7, 121.2, 121.1, 120.8, 48.1, 48.0, 45.15, 45.14, 26.3, 25.8, 24.6, 24.3.
HRMS (EI) calculated for [C21H17NS]+ requires m/z 315.1076, found m/z 315.1080.
Methyl 2-phenyl-3-(quinolin-6-yl)cyclobutane-1-carboxylate (51). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (310 mg, 2.0 mmol) and methyl cinnamate (1.6 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (6:1-3:1 v/v) as the eluent to give 387 mg (1.22 mmol, 61% yield, 2.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.40-8.97 (m, 1H), 8.62-8.38 (m, 1H), 7.94 (d, J=8.4 Hz, 0.67H), 7.69 (s, 0.67H), 7.68-7.61 (m, 1H), 7.60-7.52 (m, 1.33H), 7.36-7.24 (m, 3.33H), 7.10 (dd, J=8.4, 1.6 Hz, 0.33H), 7.06-6.97 (m, 1H), 6.94-6.87 (m, 0.67H), 4.40 (t, J=9.2 Hz, 0.33H), 4.24-4.16 (m, 0.33H), 3.96 (t, J=9.8 Hz, 0.67H), 3.81-3.66 (m, 4H), 3.36-3.26 (m, 0.67H), 2.98-2.85 (m, 0.33H), 2.80-2.68 (m, 1H), 2.55-2.50 (m, 0.67H).
13C NMR (CDCl3, 100 MHz): δ 174.9, 174.4, 151.7, 151.4, 146.0, 143.9, 142.6, 142.0, 141.5, 138.5, 136.1, 135.8, 128.8, 128.6, 128.4, 128.1, 128.0, 127.5, 127.2, 127.1, 127.04, 127.00, 126.6, 126.4, 124.3, 123.7, 120.6, 52.03, 51.97, 50.7, 47.6, 43.7, 42.6, 41.5, 40.5, 29.2, 26.7.
HRMS (EI) calculated for [C21H19NO2]+ requires m/z 317.1410, found m/z 317.1411.
1-(2-Phenyl-3-(quinolin-6-yl)cyclobutyl)ethan-1-one (52). The title compound was synthesized according to the General Procedure B using 6-vinylquinoline (313 mg, 2.0 mmol) and (E)-4-phenylbut-3-en-2-one (1.5 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (6:1→3:1 v/v) as the eluent to give 361 mg (1.20 mmol, 60% yield, 2.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.22 (s, 0.67H), 9.11 (s, 0.33H), 8.49 (d, J=6.0 Hz, 0.67H), 8.45 (d, J=6.0 Hz, 0.33H), 7.92 (d, J=8.4 Hz, 0.67H), 7.69-7.57 (m, 2H), 7.54 (s, 0.33H), 7.50-7.45 (m, 0.67H), 7.39-7.28 (m, 3.33H), 7.08-6.89 (m, 2H), 4.28-4.20 (m, 0.33H), 4.15-4.08 (m, 0.33H), 3.83-3.71 (m, 1.67H), 3.46-3.37 (m, 0.67H), 2.89-2.82 (m, 0.33H), 2.73-2.66 (m, 1H), 2.50-2.42 (m, 0.67H), 2.15 (s, 0.99H), 2.11 (s, 2.01H).
13C NMR (CDCl3, 100 MHz): δ 208.3, 208.0, 151.4, 151.0, 146.4, 144.3, 142.0, 141.5, 141.4, 138.6, 136.2, 135.9, 129.1, 128.81, 128.77, 128.12, 128.09, 127.7, 127.2, 126.9, 126.6, 124.2, 123.5, 120.7, 50.6, 49.8, 48.4, 47.6, 43.0, 41.8, 28.5, 28.3, 27.8, 24.9.
HRMS (EI) calculated for [C21H19NO]+ requires m/z 301.1461, found m/z 301.1458.
4-(2-Phenylcyclobutyl)-1,1′-biphenyl (53). The title compound was synthesized according to the General Procedure B using 4-vinyl-1,1′-biphenyl (360 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes as the eluent to give 466 mg (1.64 mmol, 82% yield, 3.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.61-7.47 (m, 3.50H), 7.45-7.17 (m, 9H), 7.10-6.94 (m, 1.50H), 4.11-3.98 (m, 0.50H), 3.68-3.55 (m, 1.50H), 2.54-2.42 (m, 1H), 2.41-2.27 (m, 1.50H), 2.24-2.09 (m, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 144.5, 143.7, 141.4, 141.1, 141.0, 140.7, 139.0, 138.2, 128.7, 128.6, 128.33, 128.32, 127.9, 127.7, 127.05, 127.02, 126.99, 126.9, 126.8, 126.6, 126.3, 126.1, 126.0, 125.6, 47.9, 47.6, 45.3, 45.0, 26.0, 25.9, 24.4, 24.2.
HRMS (EI) calculated for [C22H20]+ requires m/z 284.1560, found m/z 284.1564.
Methyl 4-(2-phenylcyclobutyl)benzoate (54). The title compound was synthesized according to the General Procedure B using methyl 4-vinylbenzoate (324 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (20:1 v/v) as the eluent to give 442 mg (1.66 mmol, 83% yield, 3.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.96 (d, J=8.4 Hz, 1.50H), 7.75 (d, J=8.4 Hz, 0.50H), 7.33-7.26 (m, 3H), 7.24-7.17 (m, 2.25H), 7.10-7.04 (m, 0.50H), 7.03-6.97 (m, 0.75H), 6.94-6.89 (m, 0.50H), 4.11-3.98 (m, 0.50H), 3.89 (s, 2.25H), 3.83 (s, 0.75H), 3.67-3.53 (m, 1.50H), 2.53-2.43 (m, 1H), 2.39-2.29 (m, 1.50H), 2.23-2.11 (m, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 167.2, 167.1, 149.8, 147.2, 144.0, 140.9, 129.7, 129.0, 128.4, 128.0, 127.83, 127.78, 127.7, 127.3, 126.6, 126.5, 126.3, 125.7, 52.0, 51.8, 47.9, 47.8, 45.3, 45.2, 25.9, 25.6, 24.1, 24.0.
HRMS (EI) calculated for [C18H18O2]+ requires m/z 266.1301, found m/z 266.1306.
1-(4-(2-Phenylcyclobutyl)phenyl)ethan-1-one (55). The title compound was synthesized according to the General Procedure B using 1-(4-vinylphenyl)ethan-1-one (292 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (20:1 v/v) as the eluent to give 415 mg (1.66 mmol, 83% yield, 3.3:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.89 (d, J=8.4 Hz, 1.54H), 7.68 (d, J=8.4 Hz, 0.46H), 7.34-7.27 (m, 3.08H), 7.24-7.18 (m, 2.23H), 7.12-7.06 (m, 0.46H), 7.04-6.99 (m, 0.77H), 6.96-6.89 (m, 0.46H), 4.16-4.02 (m, 0.46H), 3.70-3.52 (m, 1.54H), 2.58 (s, 2.31H), 2.54-2.43 (m, 1.61H), 2.40-2.30 (m, 1.54H), 2.24-2.12 (m, 1.54H).
13C NMR (CDCl3, 100 MHz): δ 198.0, 197.8, 150.1, 147.6, 144.0, 140.9, 135.2, 134.6, 128.5, 128.4, 128.0, 127.84, 127.82, 127.7, 126.8, 126.5, 126.3, 125.8, 47.90, 47.86, 45.3, 45.2, 26.6, 26.5, 25.9, 25.6, 24.2, 24.1.
HRMS (EI) calculated for [C18H18O]+ requires m/z 250.1352, found m/z 250.1352.
4-(2-Phenylcyclobutyl)benzaldehyde (56). The title compound was synthesized according to the General Procedure B using 4-vinylbenzaldehyde (264 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (20:1 v/v) as the eluent to give 402 mg (1.70 mmol, 85% yield, 3.6:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.97 (s, 0.78H), 9.85 (s,0.22H), 7.81 (d, J=8.2 Hz, 1.56H), 7.59 (d, J=8.2 Hz, 0.44H), 7.40-7.19 (m, 5.44H), 7.12-6.90 (m, 1.56H), 4.16-3.98 (m, 0.44H), 3.75-3.51 (m, 1.56H), 2.58-2.45 (m, 0.88H), 2.43-2.28 (m, 1.56H), 2.27-2.11 (m, 1.56H).
13C NMR (CDCl3, 100 MHz): δ 192.1, 192.0, 151.7, 149.2, 143.8, 140.8, 134.6, 134.0, 129.9, 129.2, 128.5, 128.4, 127.8, 127.7, 127.2, 126.6, 126.4, 125.9, 47.94, 47.93, 45.41, 45.38, 26.0, 25.6, 24.1, 24.0.
HRMS (EI) calculated for [C17H16O]+ requires m/z 236.1196, found m/z 236.1202.
N,N-diethyl-4-(2-phenylcyclobutyl)benzamide (57). The title compound was synthesized according to the General Procedure B using N,N-diethyl-4-vinylbenzamide (407 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 516 mg (1.68 mmol, 84% yield, 4.7:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.33-7.17 (m, 7.36H), 7.11-6.89 (m, 1.64H), 4.17-3.94 (m, 0.36H), 3.73-2.96 (m, 5.64H), 2.56-2.42 (m, 0.72H), 2.41-2.25 (m, 1.64H), 2.22-2.06 (m, 1.64H), 1.28-1.05 (m, 6H).
13C NMR (CDCl3, 100 MHz): δ 171.5, 171.4, 145.6, 144.2, 142.6, 141.1, 135.0, 134.3, 128.3, 127.9, 127.8, 127.6, 126.60, 126.58, 126.4, 126.2, 125.6, 125.5, 47.9, 47.7, 45.3, 45.1, 43.3, 39.2, 25.9, 25.8, 23.9, 23.7, 14.1, 13.0.
HRMS (EI) calculated for [C21H25NO]+ requires m/z 307.1931, found m/z 307.1935.
Trans-1-(2-phenylcyclobutyl)naphthalene (58). The title compound was synthesized according to the General Procedure B using 1-vinylnaphthalene (308 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes as the eluent to give 362 mg (1.40 mmol, 70% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.96-7.89 (m, 1H), 7.87-7.80 (m, 1H), 7.71 (d, J=8.0 Hz, 1H), 7.53-7.39 (m, 4H), 7.35-7.26 (m, 4H), 7.23-7.15 (m, 1H), 4.27 (q, J=9.2 Hz, 1H), 3.99 (q, J=9.2 Hz, 1H), 2.71-2.59 (m, 1H), 2.50-2.39 (m, 1H), 2.33-2.21 (m, 1H), 2.16-2.04 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 144.6, 140.4, 133.7, 131.6, 128.6, 128.3, 126.7, 126.6, 126.1, 125.57, 125.55, 125.5, 124.2, 122.8, 44.8, 44.7, 28.0, 26.6.
HRMS (EI) calculated for [C20H18]+ requires m/z 258.1403, found m/z 258.1409.
Trans-1-fluoro-4-(2-phenylcyclobutyl)naphthalene (59). The title compound was synthesized according to the General Procedure B using 1-fluoro-4-vinylnaphthalene (343 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes as the eluent to give 359 mg (1.30 mmol, 65% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.13-8.10 (m, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.56-7.44 (m, 2H), 7.42-7.35 (m, 1H), 7.32-7.27 (m, 4H), 7.22-7.17 (m, 1H), 7.13-7.05 (m, 1H), 4.28-4.12 (m, 1H), 3.99-3.85 (m, 1H), 2.69-2.55 (m, 1H), 2.50-2.38 (m, 1H), 2.33-2.19 (m, 1H), 2.14-1.99 (m, 1H).
19F NMR (CDCl3, 376 MHz): δ −126.0.
13C NMR (CDCl3, 100 MHz): δ 157.5 (d, J=250.1 Hz), 144.4, 136.2 (d, J=4.2 Hz), 132.7 (d, J=4.3 Hz), 128.4, 126.6, 126.5, 126.2, 125.8 (d, J=1.9 Hz), 124.2 (d, J=2.8 Hz), 123.9 (d, J=16.1 Hz), 122.4 (d, J=8.2 Hz), 121.0 (d, J=5.8 Hz), 108.7 (d, J=19.6 Hz), 45.0, 44.4, 27.9, 26.5.
HRMS (EI) calculated for [C20H17F]+ requires m/z 276.1309, found m/z 276.1315.
2-(2-Phenylcyclobutyl)naphthalene (60). The title compound was synthesized according to the General Procedure B using 2-vinylnaphthalene (308 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes as the eluent to give 418 mg (1.62 mmol, 81% yield, 6.7:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.82-7.63 (m, 3.87H), 7.51-7.17 (m, 7.13H), 7.11-6.91 (m, 1H), 4.21-4.07 (m, 0.26H), 3.82-3.60 (m, 1.74H), 2.62-2.48 (m, 0.52H), 2.46-2.32 (m, 1.74H), 2.30-2.13 (m, 1.74H).
13C NMR (CDCl3, 100 MHz): δ 144.5, 142.0, 141.5, 139.3, 133.5, 133.2, 132.2, 131.8, 128.3, 127.9, 127.7, 127.60, 127.58, 127.5, 127.4, 127.1, 127.0, 126.6, 126.1, 125.9, 125.7, 125.6, 125.5, 125.2, 124.9, 124.7, 48.2, 47.8, 45.3, 45.2, 26.0, 25.9, 24.4, 24.3.
HRMS (EI) calculated for [C20H18]+ requires m/z 258.1403, found m/z 258.1411.
Trans-9-(2-phenylcyclobutyl)phenanthrene (61). The title compound was synthesized according to the General Procedure B using 9-vinylphenanthrene (409 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes as the eluent to give 493 mg (1.60 mmol, 80% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.71 (d, J=7.6 Hz, 1H), 8.63 (d, J=7.6 Hz, 1H), 7.97 (dd, J=8.0, 1.2 Hz, 1H), 7.84 (dd, J=7.6, 1.6 Hz, 1H), 7.72 (s, 1H), 7.66-7.50 (m, 4H), 7.37-7.28 (m, 4H), 7.22-7.18 (m, 1H), 4.33-4.20 (m, 1H), 4.18-4.04 (m, 1H), 2.77-2.63 (m, 1H), 2.54-2.44 (m, 1H), 2.35-2.24 (m, 1H), 2.19-2.05 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 144.8, 138.6, 131.8, 130.9, 130.6, 129.5, 128.8, 128.4, 126.7, 126.6, 126.4, 126.2, 126.12, 126.10, 124.8, 123.4, 123.1, 122.4, 45.0, 44.0, 28.2, 26.55.
HRMS (EI) calculated for [C24H20]+ requires m/z 308.1560, found m/z 308.1557.
4-(2-Phenylcyclobutyl)quinoline (62). The title compound was synthesized according to the General Procedure B using 4-vinylquinoline (311 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (6:1 v/v) as the eluent to give 410 mg (1.58 mmol, 79% yield, 4.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.86 (d, J=4.4 Hz, 0.82H), 8.66 (d, J=4.4 Hz, 0.18H), 8.11 (d, J=8.4 Hz, 0.82H), 7.99-7.90 (m, 0.36H), 7.84 (dd, J=8.4, 1.6 Hz, 0.82H), 7.71-7.63 (m, 0.82H), 7.62-7.56 (m, 0.18H), 7.50-7.42 (m, 1H), 7.40 (dd, J=4.4, 1.2 Hz, 0.82H), 7.35-7.19 (m, 4.18H), 7.10 (d, J=4.4 Hz, 0.18H), 6.93-6.82 (m, 0.82H), 4.78-4.68 (m, 0.18H), 4.31-4.17 (m, 1H), 3.92 (q, J=9.4 Hz, 0.82H), 2.94-2.76 (m, 0.18H), 2.74-2.59 (m, 1H), 2.56-2.26 (m, 2H), 2.22-2.10 (m, 0.82H).
13C NMR (CDCl3, 100 MHz): δ 150.4, 150.0, 149.8, 148.2, 147.7, 147.1, 143.7, 140.3, 130.0, 129.8, 129.0, 128.6, 128.5, 127.6, 127.4, 127.3, 127.0, 126.6, 126.5, 126.1, 126.0, 125.8, 124.00, 123.96, 118.9, 117.8, 46.5, 44.9, 44.1, 41.2, 27.3, 26.5, 24.4, 22.7.
HRMS (EI) calculated for [C19H17N]+ requires m/z 259.1356, found m/z 259.1360.
Trans-4-(2-phenylcyclobutyl)isoquinoline (63). The title compound was synthesized according to the General Procedure B using 4-vinylisoquinoline (311 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (5:1 v/v) as the eluent to give 322 mg (1.24 mmol, 62% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 9.13 (s, 1H), 8.57 (s, 1H), 8.02-7.92 (m, 1H), 7.84-7.76 (m, 1H), 7.66-7.53 (m, 2H), 7.36-7.27 (m, 4H), 7.24-7.18 (m, 1H), 4.18 (q, J=9.2 Hz, 1H), 3.99 (q, J=9.2 Hz, 1H), 2.67-2.57 (m, 1H), 2.52-2.41 (m, 1H), 2.40-2.27 (m, 1H), 2.26-2.13 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 151.3, 144.0, 140.2, 134.2, 133.1, 130.0, 128.4, 128.2, 126.8, 126.7, 126.4, 123.3, 45.3, 43.2, 27.1, 26.7.
HRMS (EI) calculated for [C19H17N]+ requires m/z 259.1356, found m/z 259.1354.
6-(2-Phenylcyclobutyl)isoquinoline (64). The title compound was synthesized according to the General Procedure B using 6-vinylisoquinoline (311 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (5:1 v/v) as the eluent to give 337 mg (1.30 mmol, 65% yield, 3.3:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.85 (dd, J=4.4, 1.6 Hz, 0.75H), 8.77 (dd, J=4.4, 1.6 Hz, 0.25H), 8.08 (d, J=8.0 Hz, 0.75H), 8.04 (d, J=9.2 Hz, 0.75H), 7.98 (d, J=8.4 Hz, 0.25H), 7.77 (d, J=8.8 Hz, 0.25H), 7.63-7.59 (m, 1.25H), 7.40-7.19 (m, 5.75H), 7.07-7.00 (m, 0.50H), 6.98-6.93 (m, 0.50H), 4.25-4.06 (m, 0.50H), 3.85-3.60 (m, 1.50H), 2.63-2.48 (m, 1H), 2.46-2.34 (m, 1.50H), 2.30-2.16 (m, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 149.7, 149.5, 147.2, 146.8, 144.2, 142.9, 141.0, 140.2, 135.8, 135.7, 132.8, 130.7, 129.3, 129.1, 128.4, 128.3, 128.2, 127.80, 127.78, 126.6, 126.2, 125.7, 125.4, 124.4, 121.1, 120.8, 47.9, 47.8, 45.3, 45.1, 26.0, 25.9, 24.25, 24.16.
HRMS (EI) calculated for [C19H17N]+ requires m/z 259.1356, found m/z 259.1364.
5-(2-Phenylcyclobutyl)benzo[b]thiophene (65). The title compound was synthesized according to the General Procedure B using 5-vinylbenzo[b]thiophene (320 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes as the eluent to give 423 mg (1.60 mmol, 80% yield, 3.2:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.78 (d, J=8.4 Hz, 0.76H), 7.68 (s, 0.76H), 7.54 (d, J=8.4 Hz, 0.24H), 7.45 (s, 0.24H), 7.42-7.37 (m, 0.76H), 7.32-7.16 (m, 5.76H), 7.07-7.02 (m, 0.48H), 7.00-6.94 (m, 0.76H), 6.86 (dd, J=8.4, 1.7 Hz, 0.24H), 4.20-3.94 (m, 0.48H), 3.78-3.52 (m, 1.52H), 2.58-2.44 (m, 0.96H), 2.43-2.29 (m, 1.52H), 2.26-2.10 (m, 1.52H).
13C NMR (CDCl3, 100 MHz): δ 144.5, 141.5, 140.8, 139.8, 139.4, 137.8, 137.6, 137.0, 128.3, 127.9, 127.7, 126.6, 126.5, 126.1, 125.9, 125.5, 125.1, 123.7, 123.6, 122.3, 122.2, 121.5, 121.2, 48.1, 47.9, 45.3, 45.1, 26.3, 25.8, 24.7, 24.3.
HRMS (EI) calculated for [C18H16S]+ requires m/z 264.0967, found m/z 264.0971.
2-Isopropyl-5-methylcyclohexyl 4-(2-phenylcyclobutyl)benzoate (66). The title compound was synthesized according to the General Procedure B using (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 4-vinylbenzoate (570 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (v/v 20:1) as the eluent to give 500 mg (1.28 mmol, 64% yield, 3.2:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.97 (d, J=8.4 Hz, 1.52H), 7.76 (d, J=8.4 Hz, 0.48H), 7.33-7.25 (m, 3.04H), 7.24-7.17 (m, 2.24H), 7.12-7.06 (m, 0.48H), 7.05-6.92 (m, 1.24H), 4.98-4.80 (m, 1H), 4.14-3.97 (m, 0.48H), 3.70-3.46 (m, 1.52H), 2.55-2.41 (m, 0.96H), 2.39-2.28 (m, 1.52H), 2.22-2.05 (m, 2.52H), 2.01-1.88 (m, 1H), 1.78-1.65 (m, 2H), 1.60-1.45 (m, 2H), 1.19-1.01 (m, 2H), 0.95-0.86 (m, 7H), 0.82-0.73 (m, 3H).
13C NMR (CDCl3, 100 MHz): δ 166.2, 166.1, 149.6, 147.0, 144.0, 141.1, 129.7, 129.0, 128.7, 128.4, 128.0, 127.83, 127.80, 127.77, 126.54, 126.52, 126.3, 125.7, 74.6, 74.5, 47.90, 47.87, 47.3, 47.2, 45.21, 45.15, 41.0, 40.9, 34.3, 31.41, 31.38, 26.5, 26.4, 25.9, 25.7, 24.34, 24.26, 23.6, 22.0, 20.7, 16.5.
HRMS (EI) calculated for [C27H34O2]+ requires m/z 390.2553, found m/z 390.2563.
3-(4-Methoxyphenyl)-7-(2-phenylcyclobutyl)-4H-chromen-4-one (67). The title compound was synthesized according to the General Procedure B using 3-(4-methoxyphenyl)-7-vinyl-4H-chromen-4-one (555 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (5:1 v/v) as the eluent to give 650 mg (1.70 mmol, 85% yield, 3.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.21 (d, J=8.2 Hz, 0.75H), 7.98 (d, J=8.2 Hz, 0.25H), 7.95 (s, 0.75H), 7.87 (s, 0.25H), 7.53-7.44 (m, 2H), 7.38-7.21 (m, 5H), 7.13-6.89 (m, 4H), 4.19-4.06 (m, 0.50H), 3.87-3.81 (m, 3H), 3.75-3.56 (m, 1.50H), 2.60-2.45 (m, 1H), 2.44-2.31 (m, 1.50H), 2.29-2.14 (m, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 176.4, 176.3, 159.55, 159.47, 156.4, 156.0, 152.3, 152.2, 151.2, 148.8, 143.6, 140.6, 130.1, 130.0, 128.5, 128.0, 127.7, 126.6, 126.4, 126.3, 126.0, 125.6, 125.4, 124.9, 124.7, 124.3, 124.2, 124.1, 122.7, 122.1, 116.4, 115.4, 113.94, 113.90, 55.31, 55.28, 47.9, 47.8, 45.3, 45.2, 25.9, 25.6, 24.074, 24.068.
HRMS (EI) calculated for [C26H22O3]+ requires m/z 382.1563, found m/z 382.1552.
Tert-butyl 6-cyano-5-(naphthalen-2-yl)-2-azaspiro[3.3]heptane-2-carboxylate (68). The title compound was synthesized according to the General Procedure C using tert-butyl 3-(naphthalen-2-ylmethylene)azetidine-1-carboxylate (59.2 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 67.4 mg (0.194 mmol, 97% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.93-7.80 (m, 3H), 7.74 (s, 0.44H), 7.57 (s, 0.56H), 7.55-7.47 (m, 2H), 7.39 (dd, J=8.4, 2.0 Hz, 0.44H), 7.26 (dd, J=8.4, 2.0 Hz, 0.56H), 4.18-3.84 (m, 4H), 3.66 (s, 1H), 3.62-3.51 (m, 0.44H), 3.37-3.22 (m, 0.56H), 2.83-2.56 (m, 2H), 1.48-1.24 (m, 9H).
13C NMR (CDCl3, 100 MHz): δ 156.0, 155.9, 133.6, 133.31, 133.30, 133.28, 132.73, 132.70, 129.0, 128.8, 127.9, 127.72, 127.68, 127.6, 127.0, 126.6, 126.4, 126.3, 126.2, 125.5, 125.0, 124.3, 120.5, 119.9, 79.74, 79.73, 51.7, 50.3, 40.9, 40.8, 36.4, 34.9, 28.22, 28.19, 24.6, 21.8.
HRMS (EI) calculated for [C22H24N2O2]+ requires m/z 348.1832, found m/z 348.1830.
5-(Naphthalen-2-yl)-2-thiaspiro[3.3]heptane-6-carbonitrile (69). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)thietane (42.6 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol), and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol %). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (6:1 v/v) as the eluent to give 24.4 mg (0.092 mmol, 46% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.94-7.82 (m, 3.41H), 7.61 (s, 0.59H), 7.56-7.48 (m, 2.41H), 7.39 (dd, J=8.4, 2.0 Hz, 0.59H), 3.80-3.73 (m, 1H), 3.63-3.52 (m, 1.41H), 3.34-3.16 (m, 2H), 3.08 (d, J=9.2 Hz, 0.59H), 3.03 (d, J=9.8 Hz, 0.41H), 2.90-2.73 (m, 2H), 2.60-2.52 (m, 0.59H).
13C NMR (CDCl3, 100 MHz): δ 133.5, 133.34, 133.28, 133.1, 132.8, 132.7, 128.8, 128.6, 128.0, 127.8, 127.73, 127.67, 127.2, 126.6, 126.4, 126.3, 126.2, 125.6, 125.5, 124.9, 120.7, 120.3, 54.9, 53.1, 50.6, 50.3, 39.8, 38.7, 38.2, 36.9, 34.3, 32.7, 23.6, 21.0.
HRMS (EI) calculated for [C17H15NS]+ requires m/z 265.0920, found m/z 265.0918.
5-(Naphthalen-2-yl)-2-oxaspiro[3.3]heptane-6-carbonitrile (70). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.3 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 47.4 mg (0.190 mmol, 95% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.91 (d, J=8.4 Hz, 1H), 7.88-7.81 (m, 2H), 7.64-7.60 (m, 1H), 7.56-7.47 (m, 2H), 7.36 (dd, J=8.4, 2.0 Hz, 1H), 4.83 (d, J=7.2 Hz, 1H), 4.75 (d, J=7.2 Hz, 1H), 4.46 (d, J=6.8 Hz, 1H), 4.42 (d, J=6.8 Hz, 1H), 4.02 (d, J=9.8 Hz, 1H), 3.25 (q, J=9.4 Hz, 1H), 2.79-2.60 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 133.8, 133.3, 132.8, 129.0, 127.8, 127.7, 126.7, 126.3, 125.6, 124.4, 120.7, 81.0, 78.0, 51.6, 46.2, 34.2, 22.0.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.92 (d, J=8.4 Hz, 1H), 7.89-7.82 (m, 2H), 7.77 (s, 1H), 7.55-7.46 (m, 2H), 7.42 (dd, J=8.4, 2.0 Hz, 1H), 4.87 (d, J=6.8 Hz, 1H), 4.80 (d, J=6.8 Hz, 1H), 4.67 (q, J=7.2 Hz, 2H), 4.00 (d, J=8.8 Hz, 1H), 3.59-3.49 (m, 1H), 2.92-2.75 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 133.4, 133.3, 132.8, 128.9, 127.9, 127.7, 127.0, 126.5, 126.3, 125.0, 120.0, 82.5, 78.9, 50.0, 46.2, 35.8, 24.6.
HRMS (EI) calculated for [C17H15NO]+ requires m/z 249.1148, found m/z 249.1152.
1-(Naphthalen-1-yl)spiro[3.3]heptane-2-carbonitrile (71). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-1-ylmethylene)oxetane (39.4 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 47.4 mg (0.190 mmol, 95% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.11 (d, J=8.2 Hz, 1H), 7.92 (d, J=8.2 Hz, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.64-7.45 (m, 3H), 7.19 (d, J=7.2 Hz, 1H), 4.98 (d, J=7.2 Hz, 1H), 4.76-4.65 (m, 2H), 4.37 (d, J=6.6 Hz, 1H), 4.19 (d, J=6.6 Hz, 1H), 3.42 (q, J=8.8 Hz, 1H), 2.88-2.68 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 133.8, 133.3, 132.8, 129.0, 127.8, 127.7, 126.7, 126.3, 125.6, 124.4, 120.7, 81.0, 78.0, 51.6, 46.2, 34.2, 22.0.
HRMS (EI) calculated for [C17H15NO]+ requires m/z 249.1148, found m/z 249.1139.
1-([1,1′-Biphenyl]-4-yl)spiro[3.3]heptane-2-carbonitrile (72). The title compound was synthesized according to the General Procedure C using 3-([1,1′-biphenyl]-4-ylmethylene)oxetane (44.6 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (2:1 v/v) as the eluent to give 46.3 mg (0.168 mmol, 84% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.65 (d, J=8.2 Hz, 2H), 7.62-7.56 (m, 2H), 7.50-7.42 (m, 2H), 7.40-7.33 (m, 1H), 7.29 (d, J=8.2 Hz, 2H), 4.78 (d, J=7.2 Hz, 1H), 4.73 (d, J=7.2 Hz, 1H), 4.53-4.44 (m, 2H), 3.90 (d, J=9.8 Hz, 1H), 3.15 (q, J=9.4 Hz, 1H), 2.78-2.57 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 140.9, 140.3, 135.2, 128.9, 127.8, 127.6, 127.2, 127.0, 120.6, 80.9, 78.0, 51.3, 46.2, 34.2, 22.1.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.65 (d, J=8.0 Hz, 2H), 7.61 (d, J=7.4 Hz, 2H), 7.49-7.42 (m, 2H), 7.42-7.32 (m, 3H), 4.83 (d, J=6.8 Hz, 1H), 4.77 (d, J=6.8 Hz, 1H), 4.73 (d, J=7.2 Hz, 1H), 4.65 (d, J=7.2 Hz, 1H), 3.87 (d, J=8.8 Hz, 1H), 3.49 (q, J=8.0 Hz, 1H), 2.80 (d, J=7.6 Hz, 2H).
13C NMR (CDCl3, 100 MHz): δ 140.7, 140.4, 134.7, 128.8, 128.1, 127.7, 127.5, 127.1, 120.0, 82.4, 78.8, 49.5, 46.2, 35.7, 24.7.
HRMS (EI) calculated for [C19H17NO]+ requires m/z 275.1305, found m/z 275.1311.
1-(4-Chlorophenyl)spiro[3.3]heptane-2-carbonitrile (73). The title compound was synthesized according to the General Procedure C using 3-(4-chlorobenzylidene)oxetane (36.2 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol), and UiO-69-phen(binap)Cu (11.9 mg, 2.0 μmol based on Cu, 1.0 mol %). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (3:1 v/v) as the eluent to give 18.7 mg (0.080 mmol, 40% yield, 1.1:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.46-7.36 (m, 2H), 7.25 (d, J=8.4 Hz, 1H), 7.17 (d, J=8.4 Hz, 1H), 4.77 (d, J=3.2 Hz, 1H), 4.72 (s, 1H), 4.63 (d, J=3.2 Hz, 1H), 4.47 (d, J=6.6 Hz, 0.50H), 4.40 (d, J=6.6 Hz, 0.50H), 3.83 (t, J=9.2 Hz, 1H), 3.57-3.41 (m, 0.50H), 3.11-3.02 (m, 0.50H), 2.87-2.55 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 134.7, 134.3, 133.89, 133.88, 129.3, 129.2, 129.0, 128.1, 120.3, 119.7, 82.2, 80.8, 78.6, 77.7, 50.9, 49.2, 46.1, 35.5, 34.0, 24.6, 22.1.
HRMS (EI) calculated for [C13H12ClNO]+ requires m/z 233.0602, found m/z 233.0605.
1-(4-Formylphenyl)spiro[3.3]heptane-2-carbonitrile (74). The title compound was synthesized according to the General Procedure C using 4-(oxetan-3-ylidenemethyl)benzaldehyde (34.8 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol), and UiO-69-phen(binap)Cu (5.9 mg, 1.0 μmol based on Cu, 0.5 mol %). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1→1:1 v/v) as the eluent to give 27.3 mg (0.120 mmol, 60% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 10.05 (s, 1H), 7.96 (d, J=8.0 Hz, 2H), 7.43 (d, J=8.0 Hz, 2H), 4.82-4.71 (m, 2H), 4.50 (d, J=6.8 Hz, 1H), 4.37 (d, J=6.8 Hz, 1H), 3.97 (d, J=10.0 Hz, 1H), 3.18 (q, J=9.4 Hz, 1H), 2.78-2.60 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 191.4, 143.0, 135.9, 130.4, 127.4, 120.1, 80.8, 77.7, 51.3, 46.2, 34.0, 21.9.
Minor: 1H NMR (CDCl3, 400 MHz): δ 10.04 (s, 1H), 7.97 (d, J=8.0 Hz, 2H), 7.51 (d, J=8.0 Hz, 2H), 4.88-4.75 (m, 2H), 4.70-4.58 (m, 2H), 3.94 (d, J=8.8 Hz, 1H), 3.59-3.48 (m, 1H), 2.86-2.73 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 191.6, 142.6, 135.8, 130.3, 128.3, 119.5, 82.1, 78.6, 49.6, 46.1, 35.5, 24.5.
HRMS (EI) calculated for [C14H13NO2]+ requires m/z 227.0941, found m/z 227.0939.
1-(4-Acetylphenyl)spiro[3.3]heptane-2-carbonitrile (75). The title compound was synthesized according to the General Procedure C using 1-(4-(oxetan-3-ylidenemethyl)phenyl)ethan-1-one (37.7 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (2:1 v/v) as the eluent to give 44.9 mg (0.186 mmol, 93% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 8.03 (d, J=8.0 Hz, 2H), 7.35 (d, J=8.0 Hz, 2H), 4.83-4.69 (m, 2H), 4.48 (d, J=6.8 Hz, 1H), 4.37 (d, J=6.8 Hz, 1H), 3.94 (d, J=9.8 Hz, 1H), 3.16 (q, J=9.4 Hz, 1H), 2.78-2.59 (m, 5H).
13C NMR (CDCl3, 100 MHz): δ 197.3, 141.5, 136.6, 129.1, 126.9, 120.2, 80.8, 77.7, 51.2, 46.2, 34.1, 26.6, 21.9.
Minor: 1H NMR (CDCl3, 400 MHz): δ 8.03 (d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 4.81 (q, J=6.8 Hz, 2H), 4.64 (d, J=2.0 Hz, 2H), 3.91 (d, J=8.8 Hz, 1H), 3.57-3.44 (m, 1H), 2.86-2.74 (m, 2H), 2.63 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 197.4, 141.1, 136.6, 129.0, 127.9, 119.6, 82.2, 78.6, 49.6, 46.1, 35.5, 26.6, 24.5.
HRMS (EI) calculated for [C15H15NO2]+ requires m/z 241.1097, found m/z 241.1103.
Methyl 4-(2-cyanospiro[3.3]heptan-1-yl)benzoate (76). The title compound was synthesized according to the General Procedure C using methyl 4-(oxetan-3-ylidenemethyl)benzoate (40.7 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (2:1 v/v) as the eluent to give 39.7 mg (0.154 mmol, 77% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 8.10 (d, J=8.4 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 4.80-4.70 (m, 2H), 4.47 (d, J=6.8 Hz, 1H), 4.36 (d, J=6.8 Hz, 1H), 3.96-3.90 (m, 4H), 3.15 (q, J=9.4 Hz, 1H), 2.77-2.57 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 166.5, 141.3, 130.4, 129.8, 126.7, 120.3, 80.8, 77.7, 52.2, 51.2, 46.2, 34.1, 21.9.
Minor: 1H NMR (CDCl3, 400 MHz): δ 8.11 (d, J=8.4 Hz, 2H), 7.40 (d, J=8.4 Hz, 2H), 4.85-4.76 (m, 2H), 4.63 (s, 2H), 3.93 (s, 3H), 3.90 (d, J=8.8 Hz, 1H), 3.56-3.44 (m, 1H), 2.84-2.73 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 166.6, 140.9, 130.3, 129.8, 127.7, 119.6, 82.3, 78.6, 52.2, 49.7, 46.1, 35.6, 24.5.
HRMS (EI) calculated for [C15H15NO3]+ requires m/z 257.1046, found m/z 257.1045.
Ethyl 1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (77). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.3 mg, 0.2 mmol) and ethyl acrylate (64 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (7:1 v/v) as the eluent to give 55.7 mg (0.188 mmol, 94% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.90-7.76 (m, 3H), 7.68 (s, 0.40H), 7.62 (s, 0.60H), 7.52-7.40 (m, 2.40H), 7.28 (dd, J=8.4, 1.6 Hz, 0.60H), 4.90-4.79 (m, 1.60H), 4.74 (d, J=6.8 Hz, 0.40H), 4.66 (s, 1.20H), 4.46 (d, J=6.6 Hz, 0.40H), 4.41 (d, J=6.4 Hz, 0.40H), 4.20-4.11 (m, 0.80H), 4.04 (d, J=9.8 Hz, 0.60H), 3.92 (d, J=9.2 Hz, 0.40H), 3.82-3.73 (m, 1.20H), 3.56-3.45 (m, 0.60H), 3.30 (q, J=9.0 Hz, 0.40H), 2.90 (dd, J=12.6, 7.0 Hz, 0.60H), 2.61-2.48 (m, 1.40H), 1.24 (t, J=7.2 Hz, 1.20H), 0.79 (t, J=7.2 Hz, 1.80H).
13C NMR (CDCl3, 100 MHz): δ 173.8, 173.0, 136.1, 135.4, 133.44, 133.35, 132.5, 132.3, 128.5, 128.1, 127.71, 127.66, 127.6, 127.5, 126.4, 126.2, 126.1, 125.8, 125.7, 125.6, 125.5, 125.3, 83.6, 81.8, 79.6, 78.8, 60.8, 60.3, 51.1, 50.1, 44.86, 44.84, 39.4, 37.6, 33.4, 33.0, 14.2, 13.7.
HRMS (EI) calculated for [C19H20O3]+ requires m/z 296.1407, found m/z 296.1408.
Benzyl 1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (78). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and benzyl acrylate (97.3 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (7:1 v/v) as the eluent to give 63.8 mg (0.178 mmol, 89% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.90-7.70 (m, 3H), 7.67 (s, 0.40H), 7.59 (s, 0.60H), 7.52-7.38 (m, 2.40H), 7.34-7.26 (m, 2H), 7.22 (dd, J=8.4, 1.8 Hz, 0.60H), 7.15-7.07 (m, 0.60H), 7.03-6.94 (m, 1.20H), 6.80-6.72 (m, 1.20H), 5.13 (s, 0.80H), 4.87-4.77 (m, 1.60H), 4.76-4.66 (m, 1.60H), 4.60 (s, 1.20H), 4.45 (d, J=6.6 Hz, 0.40H), 4.41 (d, J=6.6 Hz, 0.40H), 4.03 (d, J=9.8 Hz, 0.60H), 3.93 (d, J=9.2 Hz, 0.40H), 3.62-3.50 (m, 0.60H), 3.36 (q, J=9.1 Hz, 0.40H), 2.94 (dd, J=12.7, 7.3 Hz, 0.60H), 2.63-2.47 (m, 1.40H).
13C NMR (CDCl3, 100 MHz): δ 173.6, 172.8, 135.9, 135.7, 135.3, 135.1, 133.4, 132.5, 132.4, 128.5, 128.23, 128.19, 128.17, 128.1, 128.0, 127.9, 127.8, 127.7, 127.62, 127.56, 126.7, 126.2, 126.1, 125.8, 125.72, 125.68, 125.22, 125.20, 83.6, 81.7, 79.6, 78.7, 66.5, 66.4, 51.3, 50.2, 44.9, 44.7, 39.4, 37.6, 33.5, 32.9.
HRMS (EI) calculated for [C24H22O3]+ requires m/z 358.1563, found m/z 358.1568.
Prop-2-yn-1-yl 1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (79). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.0 mg, 0.2 mmol) and prop-2-yn-1-yl acrylate (66.1 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (8:1 v/v) as the eluent to give 42.9 mg (0.140 mmol, 70% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.91-7.76 (m, 3H), 7.70-7.65 (m, 0.40H), 7.63-7.59 (m, 0.60H), 7.53-7.38 (m, 2.40H), 7.28 (dd, J=8.4, 2.0 Hz, 0.60H), 4.89 (d, J=6.4 Hz, 0.60H), 4.87-4.80 (m, 1H), 4.78-4.64 (m, 2.40H), 4.47 (d, J=6.4 Hz, 0.40H), 4.41 (d, J=6.4 Hz, 0.40H), 4.40-4.31 (m, 0.60H), 4.31-4.22 (m, 0.60H), 4.14-4.02 (m, 0.60H), 3.95 (d, J=9.3 Hz, 0.40H), 3.64-3.52 (m, 0.60H), 3.37 (q, J=9.1 Hz, 0.40H), 2.99-2.89 (m, 0.60H), 2.63-2.53 (m, 1.40H), 2.47 (t, J=2.4 Hz, 0.40H), 2.03 (t, J=2.4 Hz, 0.60H).
13C NMR (CDCl3, 100 MHz): δ 173.0, 172.2, 135.7, 135.0, 133.4, 132.5, 132.4, 128.6, 128.3, 127.9, 127.8, 127.7, 127.5, 126.5, 126.3, 126.1, 125.9, 125.8, 125.7, 125.4, 125.2, 83.5, 81.8, 79.6, 78.7, 77.4, 77.0, 75.1, 74.5, 52.3, 51.7, 51.2, 50.1, 44.9, 44.8, 39.3, 37.3, 33.4, 33.0.
HRMS (EI) calculated for [C20H18O3]+ requires m/z 306.1250, found m/z 306.1245.
Ethyl 2-methyl-1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (80). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and ethyl methacrylate (75 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (10:1 v/v) as the eluent to give 54.6 mg (0.176 mmol, 88% yield, 1.2:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.88-7.80 (m, 3H), 7.75 (s, 1H), 7.52-7.44 (m, 2H), 7.36 (dd, J=8.4, 1.8 Hz, 1H), 5.00 (d, J=6.8 Hz, 1H), 4.93 (d, J=6.8 Hz, 1H), 4.87 (d, J=6.8 Hz, 1H), 4.70 (d, J=6.8 Hz, 1H), 4.23 (q, J=7.2 Hz, 2H), 4.07 (s, 1H), 2.86-2.77 (m, 1H), 2.29 (d, J=11.8 Hz, 1H), 1.32 (t, J=7.2 Hz, 3H), 1.07 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 176.8, 134.9, 133.4, 132.2, 128.1, 127.8, 127.6, 127.0, 126.2, 126.1, 125.8, 83.5, 79.5, 61.0, 53.0, 44.0, 43.0, 42.2, 19.1, 14.2.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.82-7.75 (m, 3H), 7.60-7.56 (m, 1H), 7.49-7.40 (m, 2H), 7.26-7.22 (m, 1H), 4.92 (d, J=6.4 Hz, 1H), 4.85 (d, J=6.4 Hz, 1H), 4.71-4.63 (m, 2H), 3.78-3.66 (m, 2H), 3.62 (d, J=1.6 Hz, 1H), 3.13-2.99 (m, 1H), 2.25 (dd, J=12.5, 1.8 Hz, 1H), 1.56 (s, 3H), 0.71 (t, J=7.2 Hz, 3H).
13C NMR (CDCl3, 100 MHz): δ 175.1, 135.9, 133.4, 132.2, 128.1, 127.7, 127.5, 126.1, 126.0, 125.6, 125.2, 84.0, 79.9, 60.4, 58.8, 45.7, 42.4, 41.1, 25.8, 13.6.
HRMS (EI) calculated for [C20H22O3]+ requires m/z 310.1563, found m/z 310.1565.
Methyl 2-acetamido-1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (81). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and methyl 2-acetamidoacrylate (85.9 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (10:1 v/v) as the eluent to give 54.3 mg (0.160 mmol, 80% yield, 1.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.91-7.77 (m, 3H), 7.65 (d, J=16.2 Hz, 1H), 7.56-7.44 (m, 2H), 7.36 (dd, J=8.6, 1.8 Hz, 0.50H), 7.25 (dd, J=8.6, 1.9 Hz, 0.50H), 6.80 (brs, 0.50H), 5.56 (brs, 0.50H), 4.97-4.87 (m, 2.50H), 4.77-4.71 (m, 1H), 4.67-4.59 (m, 1H), 4.15 (d, J=2.6 Hz, 0.50H), 3.81 (s, 1.50H), 3.48 (s, 1.50H), 3.30 (dd, J=13.2, 2.6 Hz, 0.50H), 3.16 (d, J=12.2 Hz, 0.50H), 2.92 (d, J=12.2 Hz, 0.50H), 2.72 (d, J=13.2 Hz, 0.50H), 2.05 (s, 1.50H), 1.68 (s, 1.50H).
13C NMR (CDCl3, 100 MHz): δ 173.3, 173.1, 170.3, 170.0, 134.6, 133.4, 132.6, 132.2, 131.7, 128.8, 128.5, 128.4, 127.9, 127.7, 127.65, 127.60, 126.7, 126.5, 126.3, 125.85, 125.75, 124.6, 124.2, 83.9, 82.2, 79.3, 78.7, 60.5, 57.5, 55.5, 52.9, 52.6, 52.4, 42.6, 42.4, 42.1, 39.5, 24.0, 22.6.
HRMS (EI) calculated for [C20H21NO4]+ requires m/z 339.1465, found m/z 339.1467.
Methyl 2-fluoro-1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylatee (82).
The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and methyl 2-fluoroacrylate (56 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (10:1 v/v) as the eluent to give 45.0 mg (0.150 mmol, 75% yield, 1.6:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.88-7.78 (m, 3.62H), 7.73 (s, 0.38H), 7.52-7.43 (m, 2.62H), 7.35 (d, J=8.4 Hz, 0.38H), 4.99 (d, J=7.4 Hz, 0.62H), 4.94-4.84 (m, 2H), 4.75 (d, J=7.4 Hz, 0.62H), 4.71-4.61 (m, 0.76H), 4.27-4.16 (m, 1H), 3.85 (s, 1.14H), 3.59 (s, 1.86H), 3.13-3.02 (m, 0.38H), 3.00-2.93 (m, 0.62H), 2.92-2.81 (m, 0.38H), 2.72-2.61 (m, 0.62H).
19F NMR (CDCl3, 376 MHz): δ −142.1, −171.7.
13C NMR (CDCl3, 100 MHz): δ 170.8 (d, J=27.1 Hz), 170.3 (d, J=27.5 Hz), 133.5, 133.3, 133.0, 132.6, 132.4, 131.1 (d, J=1.7 Hz), 128.7, 128.3, 128.1 (d, J=2.1 Hz), 127.9, 127.8, 127.64, 127.59, 126.34, 126.26, 126.13, 126.06 (d, J=2.2 Hz), 126.0, 124.8, 124.0, 92.7 (d, J=232.0 Hz), 92.5 (d, J=224.7 Hz), 82.1 (d, J=1.6 Hz), 80.9, 78.6 (d, J=2.8 Hz), 78.4, 56.1 (d, J=21.8 Hz), 55.6 (d, J=21.1 Hz), 52.9, 52.5, 42.71 (d, J=22.5 Hz), 42.70 (d, J=2.5 Hz), 41.7 (d, J=20.8 Hz), 39.4 (d, J=16.0 Hz).
HRMS (EI) calculated for [C18H17FO3]+ requires m/z 300.1156, found m/z 300.1157.
N,N-Dimethyl-1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxamide (83).
The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and N,N-dimethylacrylamide (59.5 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (1:1 v/v) as the eluent to give 44.9 mg (0.152 mmol, 76% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.88-7.75 (m, 3H), 7.62 (s, 1H), 7.51-7.42 (m, 2H), 7.38 (dd, J=8.4, 2.0 Hz, 0.40H), 7.23 (dd, J=8.4, 2.0 Hz, 0.60H), 4.86-4.77 (m, 1.60H), 4.72 (d, J=6.8 Hz, 0.40H), 4.53 (d, J=7.0 Hz, 0.60H), 4.48 (q, J=6.6 Hz, 0.80H), 4.33 (d, J=7.0 Hz, 0.60H), 4.05-3.95 (m, 1H), 3.69-3.56 (m, 0.60H), 3.44 (q, J=8.6 Hz, 0.40H), 3.33-3.21 (m, 0.60H), 2.98-2.86 (m, 2.40H), 2.64-2.48 (m, 5H).
13C NMR (CDCl3, 100 MHz): δ 172.9, 171.4, 136.7, 134.9, 133.5, 133.3, 132.49, 132.45, 131.2, 128.5, 128.1, 127.7, 127.64, 127.60, 127.5, 127.3, 126.2, 126.1, 126.0, 125.8, 125.7, 125.5, 84.1, 82.5, 79.6, 79.1, 53.0, 49.6, 44.4, 44.3, 38.1, 36.93, 36.86, 36.4, 35.6, 35.1, 33.7, 33.2.
HRMS (EI) calculated for [C19H21NO2]+ requires m/z 295.1567, found m/z 295.1566.
1-(1-(Naphthalen-2-yl)spiro[3.3]heptan-2-yl)propan-1-one (84). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and pent-1-en-3-one (50.5 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (5:1 v/v) as the eluent to give 53.8 mg (0.192 mmol, 96% yield, 1.3:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.96-7.73 (m, 3H), 7.64 (s, 0.46H), 7.55 (s, 0.54H), 7.53-7.42 (m, 2H), 7.38 (dd, J=8.4, 1.8 Hz, 0.46H), 7.08 (dd, J=8.4, 1.8 Hz, 0.54H), 4.87 (d, J=6.2 Hz, 0.54H), 4.82 (d, J=6.2 Hz, 0.54H), 4.75 (d, J=6.8 Hz, 0.46H), 4.68 (d, J=6.8 Hz, 0.46H), 4.52 (d, J=7.0 Hz, 0.54H), 4.47 (d, J=6.5 Hz, 0.46H), 4.43-4.34 (m, 1H), 4.10 (d, J=10.1 Hz, 0.54H), 3.76 (d, J=9.1 Hz, 0.46H), 3.70-3.57 (m, 0.54H), 3.46 (q, J=8.9 Hz, 0.46H), 3.20-3.08 (m, 0.54H), 2.58-2.38 (m, 2.46H), 2.06-1.78 (m, 1H), 1.02 (t, J=7.3 Hz, 1.62H), 0.62 (t, J=7.3 Hz, 1.38H).
13C NMR (CDCl3, 100 MHz): δ 210.5, 210.3, 136.1, 135.1, 133.5, 133.4, 132.6, 132.4, 128.7, 128.5, 127.7, 127.6, 127.3, 126.4, 126.3, 126.0, 125.92, 125.90, 125.52, 125.47, 84.4, 81.9, 79.4, 78.9, 53.2, 50.1, 45.8, 44.3, 43.9, 35.0, 34.5, 32.3, 32.2, 7.5, 7.2.
HRMS (EI) calculated for [C19H20O2]+ requires m/z 280.1458, found m/z 280.1459.
4,4,5,5-Tetramethyl-2-(1-(naphthalen-2-yl)spiro[3.3]heptan-2-yl)-1,3,2-dioxaborolane (85). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (92.5 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (20:1 v/v) as the eluent to give 63.7 mg (0.182 mmol, 91% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.84-7.75 (m, 3H), 7.70 (s, 1H), 7.49-7.39 (m, 3H), 4.90 (d, J=6.4 Hz, 1H), 4.83 (d, J=6.4 Hz, 1H), 4.63 (d, J=7.2 Hz, 1H), 4.59 (d, J=7.2 Hz, 1H), 3.89 (d, J=9.9 Hz, 1H), 2.57-2.48 (m, 1H), 2.47-2.37 (m, 1H), 2.35-2.24 (m, 1H), 0.94 (s, 6H), 0.93 (s, 6H).
13C NMR (CDCl3, 100 MHz): δ 139.2, 133.4, 132.1, 127.9, 127.55, 127.54, 125.89, 125.85, 125.6, 125.2, 84.0, 83.2, 80.3, 49.2, 47.0, 32.3, 24.7, 24.6.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.90-7.78 (m, 3H), 7.64 (s, 1H), 7.51-7.40 (m, 3H), 4.82 (d, J=6.8 Hz, 1H), 4.70 (d, J=6.8 Hz, 1H), 4.43 (d, J=6.4 Hz, 1H), 4.39 (d, J=6.4 Hz, 1H), 3.72 (d, J=9.6 Hz, 1H), 2.43-2.24 (m, 2H), 2.03 (q, J=9.5 Hz, 1H), 1.24 (s, 12H).
13C NMR (CDCl3, 100 MHz): δ 138.7, 133.6, 132.3, 128.1, 127.7, 127.6, 126.0, 125.8, 125.44, 125.41, 83.4, 82.6, 79.7, 48.5, 48.1, 31.5, 24.75, 24.68.
HRMS (EI) calculated for [C22H27BO3]+ requires m/z 350.2048, found m/z 350.2052.
5-(Naphthalen-2-yl)-6,6-diphenyl-2-oxaspiro[3.3]heptane (86). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and styrene (68 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (20:1 v/v) as the eluent to give 58.9 mg (0.196 mmol, 98% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.92-7.78 (m, 1.20H), 7.72-7.64 (m, 1.60H), 7.56-7.44 (m, 1.80H), 7.42-7.34 (m, 1.80H), 7.30-7.17 (m, 2H), 7.09-7.01 (m, 1.20H), 7.00-6.94 (m, 0.60H), 6.93-6.85 (m, 1.80H), 5.04 (d, J=6.0 Hz, 0.60H), 4.97 (d, J=6.0 Hz, 0.60H), 4.85 (d, J=6.7 Hz, 0.40H), 4.74 (d, J=6.7 Hz, 0.40H), 4.62-4.50 (m, 1.40H), 4.44 (d, J=6.9 Hz, 0.60H), 4.21-4.15 (m, 0.60H), 4.10-3.98 (m, 0.60H), 3.82-3.67 (m, 0.80H), 3.07-2.98 (m, 0.60H), 2.92-2.83 (m, 0.60H), 2.80-2.70 (m, 0.40H), 2.45-2.31 (m, 0.40H).
13C NMR (CDCl3, 100 MHz): δ 143.6, 140.2, 137.1, 135.7, 133.5, 133.2, 132.5, 131.9, 128.5, 128.4, 127.8, 127.72, 127.71, 127.66, 127.6, 127.5, 127.4, 127.2, 126.8, 126.4, 126.2, 125.9, 125.82, 125.78, 125.7, 125.6, 125.3, 85.3, 81.4, 79.4, 79.2, 55.2, 53.8, 44.9, 43.6, 38.9, 38.4, 37.2, 36.7.
HRMS (EI) calculated for [C22H20O]+ requires m/z 300.1509, found m/z 300.1508.
5-(Naphthalen-2-yl)-6-(p-tolyl)-2-oxaspiro[3.3]heptane (87). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-methyl-4-vinylbenzene (77 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (20:1 v/v) as the eluent to give 57.2 mg (0.182 mmol, 91% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.91-7.76 (m, 1.20H), 7.72-7.63 (m, 1.60H), 7.54 (d, J=8.5 Hz, 0.60H), 7.51-7.33 (m, 3H), 7.16-7.05 (m, 1.60H), 6.90 (dd, J=8.5, 1.8 Hz, 0.60H), 6.85 (d, J=8.0 Hz, 1.20H), 6.78 (d, J=8.0 Hz, 1.20H), 5.02 (d, J=5.9 Hz, 0.60H), 4.96 (d, J=6.0 Hz, 0.60H), 4.84 (d, J=6.7 Hz, 0.40H), 4.73 (d, J=6.7 Hz, 0.40H), 4.61-4.50 (m, 1.40H), 4.44 (d, J=6.9 Hz, 0.60H), 4.14 (dd, J=9.3, 3.0 Hz, 0.60H), 3.99 (q, J=9.4 Hz, 0.60H), 3.77-3.62 (m, 0.80H), 3.03-2.95 (m, 0.60H), 2.89-2.80 (m, 0.60H), 2.78-2.69 (m, 0.40H), 2.37-2.28 (m, 1.60H), 2.14 (s, 1.80H).
13C NMR (CDCl3, 100 MHz): δ 140.5, 137.2, 137.1, 135.9, 135.0, 133.5, 133.3, 132.5, 131.9, 129.1, 128.5, 128.4, 127.70, 127.68, 127.64, 127.60, 127.5, 127.4, 127.1, 126.9, 126.3, 126.1, 125.9, 125.8, 125.7, 125.6, 125.3, 85.3, 81.5, 79.4, 79.2, 55.1, 53.9, 44.9, 43.6, 38.7, 38.2, 37.4, 36.9, 21.0, 20.9.
HRMS (EI) calculated for [C23H22O]+ requires m/z 314.1665, found m/z 314.1665.
5-(Naphthalen-2-yl)-6-(4-(trifluoromethyl)phenyl)-2-oxaspiro[3.3]heptane (88). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-(trifluoromethyl)-4-vinylbenzene (103 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (8:1 v/v) as the eluent to give 60.4 mg (0.164 mmol, 82% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.94-7.80 (m, 3H), 7.71-7.66 (m, 1H), 7.57-7.44 (m, 5H), 7.36-7.29 (m, 2H), 4.85 (d, J=6.8 Hz, 1H), 4.74 (d, J=6.8 Hz, 1H), 4.60 (d, J=6.2 Hz, 1H), 4.53 (d, J=6.2 Hz, 1H), 3.88-3.67 (m, 2H), 2.88-2.76 (m, 1H), 2.46-2.29 (m, 1H).
19F NMR (CDCl3, 376 MHz): δ −62.38.
13C NMR (CDCl3, 100 MHz): δ 147.6, 136.4, 133.5, 132.6, 130.9, 128.68 (q, J=32.3 Hz), 128.66, 127.7, 126.7, 126.4, 125.90, 125.86, 125.6, 125.4 (q, J=3.7 Hz), 124.2 (q, J=270.2 Hz), 81.2, 79.0, 53.8, 45.0, 38.3, 37.0.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.74-7.66 (m, 2H), 7.55 (d, J=8.6 Hz, 1H), 7.46-7.37 (m, 3H), 7.30 (d, J=8.0 Hz, 2H), 7.00 (d, J=8.0 Hz, 2H), 6.85 (dd, J=8.6, 1.8 Hz, 1H), 5.05 (d, J=6.0 Hz, 1H), 4.98 (d, J=6.0 Hz, 1H), 4.55 (d, J=7.0 Hz, 1H), 4.43 (d, J=7.0 Hz, 1H), 4.24-4.20 (m, 1H), 4.11-4.06 (m, 1H), 3.09-2.90 (m, 2H).
19F NMR (CDCl3, 376 MHz): δ −62.36.
13C NMR (CDCl3, 100 MHz): δ 144.6, 135.1, 133.3, 132.0, 127.9 (q, J=18.2 Hz), 127.9, 127.8, 127.54, 127.53, 127.4, 126.4, 126.1, 125.6, 124.8 (q, J=3.8 Hz), 124.1 (q, J=272.0 Hz), 85.1, 79.3, 55.2, 43.6, 38.8, 36.9.
HRMS (EI) calculated for [C23H19F3O]+ requires m/z 368.1383, found m/z 368.1374.
6-(4-Chlorophenyl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (89). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-chloro-4-vinylbenzene (83.2 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (20:1 v/v) as the eluent to give 58.8 mg (0.176 mmol, 88% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
Major: 1H NMR (CDCl3, 400 MHz): δ 7.95-7.81 (m, 3H), 7.71 (s, 1H), 7.56-7.46 (m, 3H), 7.31-7.24 (m, 2H), 7.20-7.15 (m, 2H), 4.87 (d, J=6.8 Hz, 1H), 4.77 (d, J=6.8 Hz, 1H), 4.62 (d, J=6.2 Hz, 1H), 4.55 (d, J=6.2 Hz, 1H), 3.81-3.61 (m, 2H), 2.85-2.76 (m, 1H), 2.42-2.31 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 142.0, 136.7, 133.5, 132.6, 132.1, 128.6, 128.5, 127.74, 127.70, 126.3, 125.9, 125.8, 125.7, 81.3, 79.1, 53.9, 45.0, 38.0, 37.2.
Minor: 1H NMR (CDCl3, 400 MHz): δ 7.74-7.65 (m, 2H), 7.56 (d, J=8.4 Hz, 1H), 7.46-7.35 (m, 3H), 7.03-6.97 (m, 2H), 6.89-6.78 (m, 3H), 5.03 (d, J=6.0 Hz, 1H), 4.97 (d, J=6.0 Hz, 1H), 4.55 (d, J=6.8 Hz, 1H), 4.44 (d, J=6.8 Hz, 1H), 4.17 (dd, J=9.2, 3.2 Hz, 1H), 3.99 (q, J=9.4 Hz, 1H), 3.04-2.94 (m, 1H), 2.93-2.81 (m, 1H).
13C NMR (CDCl3, 100 MHz): δ 138.8, 135.4, 133.2, 132.0, 131.4, 128.5, 127.9, 127.8, 127.7, 127.6, 127.5, 126.6, 126.0, 125.5, 85.2, 79.3, 55.2, 43.5, 38.4, 36.9.
HRMS (EI) calculated for [C22H19ClO]+ requires m/z 334.1119, found m/z 334.1112.
6-(4-Fluorophenyl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (90). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-fluoro-4-vinylbenzene (73.3 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (8:1 v/v) as the eluent to give 63.1 mg (0.198 mmol, 99% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.90-7.65 (m, 3H), 7.54 (d, J=8.4 Hz, 0.57H), 7.49-7.43 (m, 1.14H), 7.43-7.35 (m, 1.43H), 7.20-7.13 (m, 0.86H), 6.99-6.68 (m, 4H), 5.03 (d, J=6.0 Hz, 0.57H), 4.96 (d, J=6.0 Hz, 0.57H), 4.83 (d, J=6.8 Hz, 0.43H), 4.72 (d, J=6.8 Hz, 0.43H), 4.61-4.54 (m, 1H), 4.51 (d, J=6.2 Hz, 0.43H), 4.46 (d, J=6.9 Hz, 0.57H), 4.14 (dd, J=9.4, 3.0 Hz, 0.57H), 3.98 (q, J=9.5 Hz, 0.57H), 3.75-3.61 (m, 0.86H), 3.03-2.93 (m, 0.57H), 2.91-2.81 (m, 0.57H), 2.80-2.71 (m, 0.43H), 2.43-2.17 (m, 0.43H).
19F NMR (CDCl3, 376 MHz): δ −116.6, −117.3.
13C NMR (CDCl3, 100 MHz): δ 161.4 (d, J=244.4 Hz), 160.9 (d, J=243.9 Hz), 139.2 (d, J=3.3 Hz), 136.7, 135.9 (d, J=3.2 Hz), 135.5, 133.5, 133.2, 132.5, 131.9, 128.6, 128.5, 127.8 (d, J=7.9 Hz), 127.7, 127.5 (d, J=6.0 Hz), 126.7, 126.2, 125.90, 125.87, 125.7, 125.5, 115.2 (d, J=21.2 Hz), 114.6 (d, J=21.2 Hz), 85.2, 81.3, 79.3, 79.1, 55.2, 54.0, 44.9, 43.4, 38.3, 37.8, 37.3, 37.0.
HRMS (EI) calculated for [C22H19FO]+ requires m/z 318.1414, found m/z 318.1407.
6-(3-Fluorophenyl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (91). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-fluoro-3-vinylbenzene (73.5 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (8:1 v/v) as the eluent to give 59.2 mg (0.186 mmol, 93% yield, 1.4:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.93-7.79 (m, 1.29H), 7.73-7.61 (m, 1.57H), 7.55 (d, J=8.5 Hz, 0.57H), 7.48-7.36 (m, 2.43H), 7.25-7.17 (m, 0.57H), 7.03-6.81 (m, 2.86H), 6.72-6.56 (m, 1.71H), 5.02 (d, J=6.0 Hz, 0.57H), 4.96 (d, J=6.0 Hz, 0.57H), 4.83 (d, J=6.8 Hz, 0.43H), 4.72 (d, J=6.8 Hz, 0.43H), 4.60-4.48 (m, 1.43H), 4.43 (d, J=6.9 Hz, 0.57H), 4.16 (dd, J=9.3, 3.0 Hz, 0.57H), 4.01 (q, J=9.5 Hz, 0.57H), 3.79-3.64 (m, 0.86H), 3.04-2.94 (m, 0.57H), 2.91-2.82 (m, 0.57H), 2.82-2.65 (m, 0.43H), 2.42-2.27 (m, 0.43H).
19F NMR (CDCl3, 376 MHz): δ −113.1, −113.8.
13C NMR (CDCl3, 100 MHz): δ 162.9 (d, J=246.0 Hz), 162.6 (d, J=245.3 Hz), 146.2 (d, J=7.0 Hz), 143.0 (d, J=7.1 Hz), 136.6, 135.3, 133.5, 133.2, 132.6, 132.0, 129.9 (d, J=8.4 Hz), 129.2 (d, J=8.3 Hz), 128.6, 127.71, 127.68, 127.6, 127.5, 126.5, 126.3, 125.90, 125.88, 125.8, 125.7, 125.5, 122.9 (d, J=2.8 Hz), 122.0 (d, J=2.7 Hz), 114.1 (d, J=21.3 Hz), 113.3 (d, J=21.0 Hz), 113.2 (d, J=21.0 Hz), 112.5 (d, J=21.1 Hz), 85.1, 81.3, 79.3, 79.0, 55.2, 53.8, 44.9, 43.5, 38.7 (d, J=1.8 Hz), 38.2 (d, J=1.8 Hz), 37.1, 36.7.
HRMS (EI) calculated for [C22H19FO]+ requires m/z 318.1414, found m/z 318.1415.
6-(2-Fluorophenyl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (92). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-fluoro-2-vinylbenzene (73.1 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (8:1 v/v) as the eluent to give 59.7 mg (0.188 mmol, 94% yield, 1.5:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.90-7.78 (m, 1.20H), 7.71-7.63 (m, 1.60H), 7.56-7.43 (m, 1.80H), 7.41-7.31 (m, 1.80H), 7.27-7.21 (m, 0.60H), 7.20-7.11 (m, 0.40H), 7.07-6.84 (m, 3H), 6.71-6.64 (m, 0.60H), 5.06 (d, J=6.0 Hz, 0.60H), 4.98 (d, J=6.0 Hz, 0.60H), 4.87 (d, J=6.8 Hz, 0.40H), 4.75 (d, J=6.8 Hz, 0.40H), 4.62-4.56 (m, 1H), 4.51 (d, J=6.3 Hz, 0.40H), 4.47 (d, J=6.9 Hz, 0.60H), 4.25-4.19 (m, 0.60H), 4.19-4.08 (m, 0.60H), 3.96-3.80 (m, 0.80H), 3.16-3.04 (m, 0.60H), 2.86-2.76 (m, 1H), 2.46-2.24 (m, 0.40H).
19F NMR (CDCl3, 376 MHz): δ −115.3, −116.9.
13C NMR (CDCl3, 100 MHz): δ 160.9 (d, J=245.3 Hz), 160.6 (d, J=245.1 Hz), 136.6, 135.6, 133.5, 133.2, 132.5, 131.9, 129.9 (d, J=15.5 Hz), 128.4, 128.0, 127.90, 127.89 (d, J=7.2 Hz), 127.88, 127.7, 127.64, 127.63 (d, J=8.2 Hz), 127.61, 127.4 (d, J=7.3 Hz), 127.3, 127.2, 127.1, 126.4, 126.2, 125.8 (d, J=4.7 Hz), 125.7, 125.6 (d, J=4.0 Hz), 125.3, 124.1 (d, J=3.5 Hz), 123.4 (d, J=3.4 Hz), 115.3 (d, J=22.0 Hz), 114.6 (d, J=21.5 Hz), 85.3, 81.4, 79.5, 79.1, 55.3 (d, J=1.3 Hz), 52.5, 45.3, 43.7, 37.2 (d, J=2.0 Hz), 35.4, 34.4 (d, J=1.6 Hz), 32.9 (d, J=1.6 Hz).
HRMS (EI) calculated for [C22H19FO]+ requires m/z 318.1414, found m/z 318.1406.
Trans-2-(5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptan-6-yl)pyridine (93). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 2-vinylpyridine (63 ptL, 0.6 mmol). The diastereomeric ratio of the trans- and cis-products in the crude reaction mixture was determined to be 1.1:1 based on 1H NMR analysis. The mixture was then purified by flash column chromatography using hexanes/ethyl acetate (5:1→2:1 v/v) as the eluent to give 54.2 mg (0.180 mmol, 90% yield, >10:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 8.59 (d, J=4.4 Hz, 1H), 7.90-7.78 (m, 3H), 7.71 (s, 1H), 7.57 (td, J=7.6, 1.8 Hz, 1H), 7.51-7.42 (m, 3H), 7.19 (d, J=7.6 Hz, 1H), 7.15-7.09 (m, 1H), 4.90 (d, J=6.8 Hz, 1H), 4.79 (d, J=6.8 Hz, 1H), 4.60 (d, J=6.2 Hz, 1H), 4.54 (d, J=6.2 Hz, 1H), 4.02 (d, J=9.8 Hz, 1H), 3.88-3.74 (m, 1H), 2.79-2.59 (m, 2H).
13C NMR (CDCl3, 100 MHz): δ 161.7, 149.6, 137.0, 136.4, 133.5, 132.5, 128.4, 127.69, 127.66, 126.2, 125.812, 125.807, 125.6, 121.9, 121.7, 81.7, 79.2, 52.6, 44.9, 40.9, 36.2.
HRMS (EI) calculated for [C21H19NO]+ requires m/z 301.1461, found m/z 301.1467.
1-Methyl-5-(5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptan-6-yl)-1H-indole (94). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-methyl-5-vinyl-1H-indole (94.3 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1→5:1 v/v) as the eluent to give 65.6 mg (0.186 mmol, 93% yield, 1.2:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.89-7.77 (m, 1.45H), 7.74 (s, 0.45H), 7.68-7.58 (m, 1.10H), 7.54-7.40 (m, 3H), 7.38-7.29 (m, 1.10H), 7.24-7.16 (m, 0.90H), 7.10 (d, J=8.4 Hz, 0.45H), 7.01-6.83 (m, 2H), 6.68 (d, J=8.4 Hz, 0.55H), 6.38 (d, J=3.2 Hz, 0.45H), 6.29 (d, J=3.2 Hz, 0.55H), 5.04 (d, J=6.0 Hz, 0.55H), 4.98 (d, J=6.0 Hz, 0.55H), 4.86 (d, J=6.8 Hz, 0.45H), 4.75 (d, J=6.8 Hz, 0.45H), 4.63-4.51 (m, 1.45H), 4.44 (d, J=6.8 Hz, 0.55H), 4.21-4.09 (m, 1.10H), 3.85-3.75 (m, 0.90H), 3.70 (s, 1.35H), 3.56 (s, 1.65H), 3.13-3.03 (m, 0.55H), 2.95-2.85 (m, 0.55H), 2.83-2.74 (m, 0.45H), 2.51-2.30 (m, 0.45H).
13C NMR (CDCl3, 100 MHz): δ 137.5, 136.3, 135.5, 135.1, 134.5, 133.7, 133.2, 132.4, 131.8, 131.1, 129.2, 128.54, 128.48, 128.3, 128.1, 127.7, 127.62, 127.57, 127.4, 127.0, 126.02, 125.97, 125.9, 125.6, 125.5, 125.1, 121.4, 120.4, 118.7, 118.0, 109.1, 108.6, 100.6, 100.4, 85.4, 81.6, 79.5, 79.4, 55.3, 54.2, 44.8, 43.7, 39.1, 38.7, 38.0, 37.2, 32.8, 32.6.
HRMS (EI) calculated for [C25H23NO]+ requires m/z 353.1774, found m/z 353.1773.
5-(5-(Naphthalen-2-yl)-2-oxaspiro[3.3]heptan-6-yl)benzofuran (95). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 5-vinylbenzofuran (86.5 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1→5:1 v/v) as the eluent to give 62.6 mg (0.184 mmol, 92% yield, 1.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.94-7.75 (m, 1.50H), 7.73 (s, 0.50H), 7.69-7.62 (m, 1H), 7.56 (d, J=2.3 Hz, 0.50H), 7.51-7.32 (m, 5H), 7.20-7.10 (m, 1.50H), 6.89 (dd, J=8.4, 1.8 Hz, 0.50H), 6.78 (d, J=8.4 Hz, 0.50H), 6.66 (d, J=2.4 Hz, 0.50H), 6.55 (d, J=2.4 Hz, 0.50H), 5.05 (d, J=6.0 Hz, 0.50H), 4.98 (d, J=6.0 Hz, 0.50H), 4.85 (d, J=6.8 Hz, 0.50H), 4.74 (d, J=6.8 Hz, 0.50H), 4.60 (d, J=6.2 Hz, 0.50H), 4.58-4.51 (m, 1H), 4.44 (d, J=6.8 Hz, 0.50H), 4.22-4.07 (m, 1H), 3.90-3.70 (m, 1H), 3.11-3.02 (m, 0.50H), 2.95-2.87 (m, 0.50H), 2.84-2.77 (m, 0.50H), 2.43-2.32 (m, 0.50H).
13C NMR (CDCl3, 100 MHz): δ 153.7, 153.3, 145.3, 144.8, 138.2, 137.1, 135.8, 134.8, 133.6, 133.2, 132.5, 131.9, 128.5, 127.72, 127.71, 127.66, 127.53, 127.48, 127.4, 127.0, 126.8, 126.2, 125.93, 125.86, 125.8, 125.7, 125.3, 123.8, 122.8, 119.2, 118.5, 111.2, 110.6, 106.40, 106.36, 85.3, 81.4, 79.4, 79.2, 55.3, 54.2, 44.9, 43.5, 38.9, 38.4, 37.7, 37.2.
HRMS (EI) calculated for [C24H20O2]+ requires m/z 340.1458, found m/z 340.1452.
6-(Benzo[b]thiophen-5-yl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (96). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 5-vinylbenzo[b]thiophene (96.0 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes/ethyl acetate (10:1→5:1 v/v) as the eluent to give 62.8 mg (0.176 mmol, 88% yield, 1.0:1 d.r.) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.91-7.72 (m, 2.50H), 7.68-7.57 (m, 1.50H), 7.53-7.31 (m, 5H), 7.28 (d, J=5.4 Hz, 0.50H), 7.23-7.18 (m, 1H), 7.13 (d, J=5.4 Hz, 0.50H), 6.90 (dd, J=8.4, 1.8 Hz, 0.50H), 6.81 (d, J=8.4 Hz, 0.50H), 5.05 (d, J=6.0 Hz, 0.50H), 4.98 (d, J=6.0 Hz, 0.50H), 4.86 (d, J=6.8 Hz, 0.50H), 4.74 (d, J=6.8 Hz, 0.50H), 4.60 (d, J=6.4 Hz, 0.50H), 4.57-4.52 (m, 1H), 4.43 (d, J=6.8 Hz, 0.50H), 4.23-4.09 (m, 1H), 3.89-3.73 (m, 1H), 3.17-3.04 (m, 0.50H), 2.98-2.88 (m, 0.50H), 2.84-2.73 (m, 0.50H), 2.45-2.30 (m, 0.50H).
13C NMR (CDCl3, 100 MHz): δ 139.8, 139.4, 137.8, 137.1, 137.0, 136.6, 135.7, 133.5, 133.2, 132.5, 131.9, 128.5, 127.8, 127.71, 127.66, 127.6, 127.5, 127.4, 126.8, 126.7, 126.20, 126.18, 125.9, 125.82, 125.78, 125.7, 125.3, 124.1, 123.62, 123.60, 123.2, 122.4, 121.74, 121.65, 120.9, 85.3, 81.4, 79.4, 79.2, 55.2, 54.0, 44.9, 43.6, 38.9, 38.4, 37.5, 37.1.
HRMS (EI) calculated for [C24H20O S]+ requires m/z 356.1229, found m/z 356.1227.
5-(Naphthalen-2-yl)-6,6-diphenyl-2-oxaspiro[3.3]heptane (97). The title compound was synthesized according to the General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and ethene-1,1-diyldibenzene (108 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexanes to hexanes/ethyl acetate (20:1 v/v) as the eluent to give 62.5 mg (0.166 mmol, 83% yield) of the title compound as a colorless oil.
1H NMR (CDCl3, 400 MHz): δ 7.77-7.64 (m, 2H), 7.57 (d, J=8.4 Hz, 1H), 7.46-7.37 (m, 5H), 7.33-7.27 (m, 2H), 7.20-7.11 (m, 1H), 7.07-6.98 (m, 3H), 6.97-6.91 (m, 2H), 6.81 (dd, J=8.4, 2.0 Hz, 1H), 4.72-4.65 (m, 2H), 4.62 (d, J=6.4 Hz, 1H), 4.55 (d, J=6.8 Hz, 2H), 3.64 (d, J=12.6 Hz, 1H), 3.16 (dd, J=12.6, 2.1 Hz, 1H).
13C NMR (CDCl3, 100 MHz): δ 150.3, 144.1, 135.6, 133.2, 132.2, 129.0, 128.4, 127.9, 127.74, 127.72, 127.44, 127.41, 127.37, 126.2, 125.89, 125.87, 125.7, 125.6, 83.9, 79.2, 59.9, 52.5, 43.8, 43.7.
HRMS (EI) calculated for [C28H24O]+ requires m/z 376.1822, found m/z 376.1812.
Stability Studies of Cu-2 and UiO-69-phen(binap)Cu
To a 25-mL flame-dried Schlenk flask cooled under N2 were added Cu-2 (2 μmol, 2.8 mg), 4-dimethylaminopyridine (0.01 mmol, 5.0 equiv.), and 1,2-dichloroethane (1.0 mL). After three freeze-pump-thaw cycles, the reaction was irradiated by three 40-watt Kessil PR160L-440 blue-LED lamps at room temperature (with three fans) for 24 hours. 1,2-Dichloroethane was then removed in vacuo and 0.6 mL of CDCl3 was added. The resulted mixture was analyzed by 1H NMR and 31P NMR. The NMR spectra showed that Cu-2 was fully degraded; only the signal of phosphine oxide was detected by 31P NMR.
To a 25-mL flame-dried Schlenk flask cooled under N2 were added UiO-69-phen(binap)Cu (2 μmol based on Cu, 11.9 mg), 4-dimethylaminopyridine (0.01 mmol, 5.0 equiv.), and 1,2-dichloroethane (1.0 mL). After three freeze-pump-thaw cycles, the reaction was irradiated by three 40-watt Kessil PR160L-440 blue-LED lamps at room temperature (with three fans) for 24 hours. After the irradiation, the solid was collected by filtration and washed with 1,2-dichloroethane. 2 mg of the dried solid was digested in a solution of D3PO4/D2O/DMSO-d6 (1:1:5 v/v/v) and subjected to 1H NMR analysis. According to the 1H NMR spectrum, Cu-2 and L3 was found to be in a ratio of 1:5.
To a 25-mL flame-dried Schlenk tube cooled under N2 atmosphere were added UiO-69-phen(binap)Cu (5.9 mg, 1 μmol based on Cu, 0.5 mol %), 4-dimethylaminopyridine (29 mg, 0.24 mmol, 1.2 equiv.), 1,2-dichloroethane (1.0 mL), 1-vinylnaphthalene (30.8 mg, 0.2 mmol), and acrylonitrile (66 ptL, 1.0 mmol) sequentially. After three freeze-pump-thaw cycles, the reaction mixture was irradiated by three 40-watt Kessil PR160L-440 blue-LED lamps at room temperature (with three fans) for 48 hours. After irradiation, the UiO-69-phen(binap)Cu was recovered by filtration, washed with anhydrous 1,2-dichloroethane (3×10 mL), and then used for subsequent cycles of the photocatalytic reaction. The filtrates were concentrated under vacuum and the yield was determined by 1H NMR analysis. The aforementioned procedure was repeated six times.
The reaction was conducted according to the general procedure A using trans-stilbene as a triplet-energy-transfer inhibitor. After the irradiation, the yield of 23 was determined by crude 1H NMR using phenyltrimethylsilane as an internal standard. The desired intermolecular crossed cycloaddition was fully suppressed.
The reaction was conducted according to the general procedure C using trans-stilbene as a triplet-energy-transfer inhibitor. After the irradiation, the yield of 70 was determined by crude 1H NMR using phenyltrimethylsilane as an internal standard. The desired intermolecular crossed cycloaddition was fully suppressed.
Kinetic Studies on the Intermolecular Crossed [2+2] Cycloaddition: For the reaction with styrene (2.0 M): to a 25-mL flame-dried Schlenk tube cooled under N2 atmosphere were added 4-phenylmorpholine (39.2 mg, 0.24 mmol), acrylonitrile (132 μL, 2.0 mmol), and styrene (0.40 mmol) sequentially. The mixture was diluted to a total volume of 0.2 mL with 1,2-dichloroethane to obtain a homogeneous solution with a styrene concentration of 2.0 M. UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol %) was added afterwards. Following three freeze-pump-thaw cycles, the reaction mixture was irradiated by three 40-watt Kessil PR160L-440 blue-LED lamps at room temperature (with three fans). 30 μL of the reaction mixture was taken out after 10, 24, 29, 34, and 48 hours, respectively. Upon solvent removal under vacuum, 0.8 mL of phenyltrimethylsilane solution (0.05 M in CDCl3) was added to the residue, and the sample was analyzed by 1H NMR using phenyltrimethylsilane as an internal standard.
For the reaction with styrene (1.5 M): the procedure was the same as previously described, except 0.30 mmol of styrene was added to the reaction.
For the reaction with styrene (1.0 M): the procedure was the same as previously described, except 0.20 mmol of styrene was added to the reaction.
For the reaction with styrene (0.5 M): the procedure was the same as previously described, except 0.10 mmol of styrene was added to the reaction.
For the reaction with styrene (0.2 M): the procedure was the same as previously described, except 0.04 mmol of styrene was added to the reaction.
The molar concentrations of product 16 were calculated based on the 1H NMR integration in reference to the internal standard. At each time point, the data represented the average of two identical experiments. The molar concentrations of product 16 were plotted against the reaction time to obtain a typical reaction kinetic profile. The reaction rates were calculated by measuring the accumulation of product 16 over a 10-to-24-hour period.
Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed invention belongs. Publications cited herein and the materials for which they are cited are specifically incorporated by reference.
Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.
This application claims the benefit of and priority to U.S. Provisional Application No. 63/604,642 filed on Nov. 30, 2023, the contents of which is incorporated herein in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63604642 | Nov 2023 | US |
