Patent Application
20240425434
The invention belongs to the technical field of chemical synthesis and in particular relates to a method for efficiently synthesizing 1,3-disubstituted allene compound at room temperature.
Allenes are a class of organic compounds containing cumulative diene functional groups. (Ref: (a) D. R. Taylor, Chem. Rev. 1967, 67, 317-359; (b) N. Krause, A. S. K. Hashmi, Modern Allene Chemistry, Wiley-VCH, Weinheim, 2004.) Due to the high reactivity and abundant reaction sites of the accumulated diene functional groups, allenes have high chemical synthesis value. At the same time, allenes are widely distributed in a variety of natural products, pharmaceutically active molecules and materials science, and are a very important class of compounds. Therefore, the efficient synthesis of allenes has always been a hot spot for synthetic chemists. The ATA (Allenation of Terminal Alkynes) reaction is a one-step method for efficiently synthesizing allenes from aldehydes or ketones, terminal alkynes, and amines. (Ref: (a) P. Crabbé, H. Fillion, D. André, J.-L. Luche, J. Chem. Soc., Chem. Commun. 1979, 859-860; (b) J. Kuang, S. Ma, J. Org. Chem. 2009, 74, 1763-1765; (c) J. Kuang, S. Ma, J. Am. Chem. Soc. 2010, 132, 1786-1787; (d) S. Kitagaki, M. Komizu, C. Mukai, Synlett 2011, 8, 1129-1132; (e) J. Kuang, H. Luo, S. Ma, Adv. Synth. Catal. 2012, 354, 933-944; (f) X. Tang, C. Zhu, T. Cao, J. Kuang, W. Lin, S. Ni, J. Zhang, S. Ma, Nat. Commun. 2013, 4, 2450; (g) X. Huang, T. Cao, Y Han, X. Jiang, W. Lin, J. Zhang, S. Ma, Chem. Commun. 2015, 51, 6956-6959. (h) D. M. Lustosa, S. Clemens, M. Rudolph, A. S. K. Hashmi, Adv. Synth. Catal. 2019, 361, 5050-5056; For an account, see: (i) X. Huang, S. Ma, Acc. Chem. Res. 2019, 52, 1301-1312.) 1979, Crabbe research group first reported this method, but since the reaction can only be applied to the synthesis of terminal allenes from paraformaldehyde and the yield is low, it has not received enough attention and development over a long period of time. In 2009, our research group optimized the conditions of Crabbe's, increased the yield of the reaction, and began to gradually broaden the scope of application of the reaction to general aldehydes and ketones. However, there are still two difficulties in the ATA reaction that have not been resolved: 1) the reaction consists of two steps, A3 coupling reaction to generate propargylamine followed by 1,5-hydrogen migration followed by β-elimination to generate allene. The step of 1,5-hydrogen migration needs to overcome a very high energy barrier, and usually needs to be carried out at a high temperature of more than one hundred degrees. Such harsh conditions not only increase energy consumption and safety hazards, but also often result in very low yields or no products for unstable allene synthesis. 2) The in situ generated water and imines in the reaction will reduce the catalytic performance of the metal species, resulting in the vast majority of cases, the metal catalysts used in the ATA reaction are not catalytic.
In order to overcome the above-mentioned problems in the prior art, the object of the present invention is to provide a method for synthesizing 1,3-disubstituted allene compound in one step at room temperature, that is, through the reaction of terminal alkynes (2), aldehydes (1) and amines (3) in an organic solvent under the action of a gold carbene catalyst and a molecular sieve, and a 1,3-disubstituted allene compound is synthesized in the next step at room temperature.
The present invention is achieved by adopting the following specific technical solutions:
The invention provides a method for synthesizing 1,3-disubstituted allene compound in one step at room temperature, comprising: terminal alkynes (2) with different substituents, aldehydes (1) and amines (3) in an organic solvent under the action of a gold carbene catalyst a and molecular sieve to generate 1,3-disubstituted allene compound at room temperature, and the reaction process is shown in the following reaction formula (a):
The functional groups in R1 and R2 are selected from carbon-carbon double bonds, halogen atoms, hydroxyl, silyl ether, carbonyl, nitrile, ester and amido groups; the said aryl groups are phenyl and polyphenyl cyclosubstituented groups with electron-donating or electron-withdrawing substituents in the ortho, meta and para positions; the said heterocyclic groups are furyl, benzofuryl, thienyl, pyridyl, indolyl and indazolyl.
Preferably,
The functional groups in R1 and R2 are selected from carbon-carbon double bonds, halogen atoms, hydroxyl, silyl ether, carbonyl, nitrile, ester and amido groups; the said aryl groups are phenyl and polyphenyl cyclosubstituented groups with electron-donating or electron-withdrawing substituents in the ortho, meta and para positions; the said electron-donating substituents comprises alkyl, methoxy, benzyloxy and boronate groups, and the said electron-withdrawing substituents comprises halogen, nitrile, ester, trifluoromethyl and nitro groups; the said heterocyclic groups are furyl, benzofuryl, thienyl, pyridyl, indolyl and indazolyl.
Further preferably,
The functional groups in R1 and R2 are selected from carbon-carbon double bonds, halogen atoms, hydroxyl, silyl ether, carbonyl, nitrile, ester and amido groups; the said aryl groups are phenyl and polyphenyl cyclosubstituented groups with electron-donating or electron-withdrawing substituents in the ortho, meta and para positions; the said electron-donating substituents comprises alkyl, methoxy, benzyloxy and boronate groups, and the said electron-withdrawing substituents comprises halogen, nitrile, ester, trifluoromethyl and nitro groups; the said heterocyclic groups are furyl, benzofuryl, thienyl, pyridyl, indolyl and indazolyl.
Further preferably,
R1 is selected from n-pentyl, isobutyl, cyclohexyl, n-octyl, phenyl, p-methoxyphenyl, p-benzyloxyphenyl, p-diboronic acid pinacol ester phenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, p-nitrilophenyl, p-esterphenyl, p-trifluoromethylphenyl, p-nitrophenyl, naphthyl, phenanthrenyl, pyrenyl, furanyl, benzofuranyl, thienyl, pyridyl, indolyl and indazolyl.
R2 is selected from cyclopropyl, n-pentyl, n-hexyl, cyclohexyl, n-octyl, n-decyl, benzyl, buten-4-yl, 4-chlorobutyl, 2-bromoethyl, (dimethyl tert-butylsiloxy) pentyl, 5-hydroxypentyl, 4-nitrilbutyl, 3-methylesterpropyl, tert-butoxycarbonyl protected piperidinyl, (p-methoxybenzoyl)propyl and phenyl.
As a further improvement, the specific operation steps of the present invention are as follows:
Under an argon atmosphere, molecular sieves, gold carbene catalysts and a certain volume of organic solvent are added in sequence to the dry reaction tube. The aldehydes (1), amines (3) and terminal alkynes (2) are then added in sequence with stirring. Reaction is carried out for 24-72 hours at room temperature. After the reaction is complete, the reaction mixture was filtered through a short silica gel column and washed with a certain volume of diethyl ether. After the mixture was concentrated, it was subjected to flash column chromatography to obtain 1,3-disubstituted allene compound.
Wherein, the organic solvent of a certain volume refers to the amount of the terminal alkynes (2) shown in the formula (a) as a benchmark, the amount of the organic solvent is 0.5-5 mL/mmol; preferably, 1 mL/mmol.
Wherein, the room temperature refers to 10-60° C.; preferably, 10-40° C.; more preferably, 25-35° C.
Wherein, the said certain volume of diethyl ether refers to the usage amount of the terminal alkynes (2) shown in the formula (a) as a benchmark, the amount of the said diethyl ether is 10-100 mL/mol; preferably, it is 30 mL/mol.
As a further improvement, the amines (3) described in the present invention is morpholine(3a), piperidine(3b), pyrrolidine(3c), 1,2,3,4-tetrahydroquinoline(3d), 1,2,3,4-tetrahydroisoquinoline(3e), 1-methyl-1,2,3,4-tetrahydroisoquinoline(3f), diethylamine(3g), diallylamine(3h), dicyclohexylamine(3i) and diisopropylamine(3j); preferably, 1-methyl-1,2,3,4-tetrahydroisoquinoline(3f).
As a further improvement, the gold carbene catalyst described in the present invention is selected from one or more of the following structures Au1-Au3. Wherein, R is C1-C30 alkyl group, C1-C30 alkyl group with functional groups, phenyl, aryl, and heterocyclic; the functional group is selected from carbon-carbon double bond, carbon-carbon triple bond, halogen atom, hydroxyl, carboxyl, amino, silyl ether, carbonyl, nitrile, ester and amido groups; the said aryl refers to phenyl and polyphenyl cyclosubstituents with electron-donating or electron-withdrawing substituents in the ortho, meta, and para positions; the electron-donating substituents include alkyl, alkoxy and boronate groups, and the electron-withdrawing substituents include halogen, nitrile, ester, trifluoromethyl and nitro groups.
Among them, X is a counter anion, including halogen anion, hydroxide anion, bis(trifluoromethanesulfonyl)imide anion, methanesulfonate anion, trifluoromethanesulfonate anion, p-methylbenzenesulfonate anion, perchlorate anion, tetrafluoroborate anion, hexafluorophosphate anion and hexafluoroantimonate anion.
Preferably, the gold carbene catalyst is Au3, and the counter anion is bis(trifluoromethanesulfonyl)imide anion.
As a further improvement, the gold carbene catalyst of the present invention is selected from one or more of Au3a, Au3b, Au3c, Au3d and Au3e; wherein, the structures of the Au3a, Au3b, Au3c, Au3d and Au3e are as follows:
As a further improvement, the molecular sieve described in the present invention is composed of 3 Å molecular sieve, 4 Å molecular sieve and 5 Å molecular sieve; preferably, is 5 Å molecular sieve.
As a further improvement, the organic solvent described in the present invention is selected from one or more of 2,2,2-trifluoroethanol, 2,2,3,3-tetrafluoropropanol, 2,2,3,3,3-pentafluoropropanol and 1,1,1,3,3,3-hexafluoroisopropanol; preferably, 2,2,2-trifluoroethanol.
As a further improvement, the molar ratio of the terminal alkynes (2), aldehydes (1), amines (3) and gold carbene catalyst is 1.0:(1.0-1.8):(1.0-1.4):(0.01-0.1); Preferably, it is 1.0:1.8:1.4:0.05.
As a further improvement, the amount of the molecular sieve used is 100-500 mg/mmol; preferably, 250 mg/mmol, based on the amount of the terminal alkynes (2).
As a further improvement, the amount of the organic solvent used is 0.5-5 mL/mmol; preferably, 1 mL/mmol, based on the amount of the terminal alkynes (2).
Under the gold carbene catalytic conditions of the present invention, the following two technical difficulties in the synthesis of 1,3-disubstituted allene compound are mainly overcome, and the reaction process is shown in the following formula (b):
1) In the known method, A3 coupling reaction generates propargyl amine compounds, and the 1,5-hydrogen migration step is the determining step, which needs to overcome a very high activation energy barrier, so the temperature of the reaction is usually at 70-200° C. This not only increases energy loss and security risks, but also often results in very low yields or no products for unstable allene synthesis.
2) The in situ generated water and imines in the reaction will reduce the catalytic performance of the metal species, resulting in the vast majority of cases, the metal catalysts used in the ATA reaction are not catalytic
The present invention can effectively overcome the above technical difficulties by developing a gold carbene catalytic method, and successfully realize the synthesis of 1,3-disubstituted allene compound at room temperature.
The present invention proposes the following possible mechanism for the reaction described in the present invention, as shown in formula (c):
The present invention also provides a class of 1,3-disubstituted allene compound, the structure of which is shown in formula 4
The definitions of R1 and R2 are the same as in the reaction formula (a).
The list of newly prepared compounds in the synthesis process of the present invention is shown in Table 1:
84%
H17 83%
H11 65%
H4, R2 = n-C8H17 R1 = 4-BrC
H4, R2 = n-C8H17
equivalent ZuI2 methylbenzene, 103° C., Ar
CC
H4, R2 = n-C10H21
H17
indicates data missing or illegible when filed
The present invention also provides the application of 1,3-disubstituted allene compound (4) in the preparation of δ-caprolactone, trans-allyl alcohol, other allene-derived compounds, and natural product molecules, as shown in Table 2:
The comparison list of the method described in the present invention and original method:
H4,
H17
indicates data missing or illegible when filed
The innovations of the present invention include:
(1) The reaction of the present invention starts from the simple and easy-to-obtain terminal alkynes(2), aldehydes(1) and amines(3), based on the gold carbene catalytic system, and undergoes A3 coupling reaction, 1,5-hydrogen migration reaction and β-elimination reaction, successfully realized the synthesis of 1,3-disubstituted allene at room temperature.
(2) The present invention uses gold carbene (Au3d) as a metal catalyst, 1-methyl-1,2,3,4-tetrahydroisoquinoline (3f) as an amine, and 2,2,2-trifluoroethanol as an organic Solvent, which successfully overcomes or breaks through the technical barriers and limitations of the original ATA reaction at high temperature, and reduces the activation energy barrier of the rate-determining step of 1,5-hydrogen migration in the ATA reaction, making the reaction proceed smoothly at room temperature.
(3) Because of the better catalytic activity of the gold carbene catalyst, under the conditions of gold carbene catalysis, this method can effectively overcome the reduction of the catalytic performance of the metal catalyst by the water and imine generated in situ during the reaction, and achieve the synthesis of 1,3-disubstituted allenes catalyzed by gold carbene at room temperature.
The beneficial effects of the present invention include: the present invention realizes for the first time by using simple and easy-to-obtain terminal alkynes (2), aldehydes (1) and amines (3) as starting materials, under the action of gold carbene catalysts, molecular sieves and organic solvents catalytic synthesis of 1,3-disubstituted allene compound at room temperature. The method of the invention reduces the energy loss and potential safety hazards in the synthesis of allenes, and is suitable for synthesizing unstable allenes. The method of the invention has the advantages of simple operation, easily available raw materials and reagents, mild reaction conditions, wide substrate universality, good functional group compatibility and strong practicability. The 1,3-disubstituted allene compound obtained in the present invention can be used as important intermediates to construct δ-caprolactone, trans-allyl alcohol, other allene-derived compounds, and natural product molecules.
The following examples are given to further illustrating the specific solutions of the present invention. The process, conditions, experimental methods, and so on for implementing the present invention are all general knowledge and common knowledge in the field except for the contents specifically mentioned below, and the present invention has no special limitation.
Wherein “mol” represents mole, “equiv.” represents equivalent, “5 Å MS” represents 5 Å molecular sieve, “TFE” represents 2,2,2-trifluoroethanol, “Ar” represents argon atmosphere, “yield” represents yield.
Under the protection of argon atmosphere, 5 Å molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol) and 2,2,2-trifluoroethanol (1 mL) were added in sequence to a dry reaction tube. Then, under stirring, aldehyde 1a (191.3 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2a (110.0 mg, 1.0 mmol) were added in sequence. After reacting at room temperature for 24 hours, the reaction solution was filtered through a short silica gel column and the filter cake was washed with diethyl ether (30 mL), concentrated, purified by flash column chromatography (eluent:petroleum ether) to afford an allene product 4aa (168.7 mg, 84% yield): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.36-7.26 (m, 4H, Ar—H), 7.22-7.14 (m, 1H, Ar—H), 6.12 (dt, J1=6.1 Hz, J2=3.0 Hz, 1H, ═CH), 5.56 (q, J=6.7 Hz, 1H, ═CH), 2.12 (qd, J1=7.1 Hz, J2=2.9 Hz, 2H, CH2), 1.53-1.41 (m, 2H, CH2), 1.41-1.18 (m, 6H, CH2×3), 0.88 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.1, 135.1, 128.5, 126.55, 126.52, 95.1, 94.5, 31.6, 29.1, 28.9, 28.7, 22.7, 14.1; IR (neat): ν=2956, 2924, 2854, 1949, 1598, 1495, 1458 cm−1; MS (FI) m/z (%): 200 (M+); HRMS Calcd. for C15H20 (M+): 200.1560, found 200.1564.
The operation is the same as Example 1. 5 Å molecular sieves (250.1 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1a (191.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2b (166.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ab (205.5 mg, 80% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.33-7.25 (m, 4H, Ar—H), 7.21-7.12 (m, 1H, Ar—H), 6.11 (dt, J1=6.1 Hz, J2=3.1 Hz, 1H, ═CH), 5.56 (q, J=6.5 Hz, 1H, ═CH), 2.12 (qd, J1=7.0 Hz, J2=2.7 Hz, 2H, CH2), 1.52-1.41 (m, 2H, CH2), 1.40-1.12 (m, 14H, CH2×7), 0.88 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.1, 135.2, 128.5, 126.56, 126.55, 95.1, 94.5, 31.9, 29.64, 29.60, 29.4, 29.3, 29.20, 29.17, 28.8, 22.7, 14.1; IR (neat): ν=2922, 2852, 1949, 1598, 1495, 1460, 1071 cm−1; MS (70 eV, EI) m/z (%): 256 (M+, 1.02), 130 (100).
The operation is the same as Example 1. 5 Å molecular sieves (251.0 mg), Au3d (43.6 mg, 0.05 mmol), aldehyde 1a (191.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2c (67.5 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ac (124.8 mg, 80% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.33-7.23 (m, 4H, Ar—H), 7.21-7.13 (m, 1H, Ar—H), 6.20 (d, J=6.0 Hz, 1H, ═CH), 5.43 (t, J=6.8 Hz, 1H, ═CH), 1.39-1.25 (m, 1H, CH), 0.80-0.68 (m, 2H, CH2), 0.51-0.37 (m, 2H, CH2); 13C NMR (100 MHz, CDCl3): δ=204.8, 134.9, 128.5, 126.8, 126.6, 99.4, 96.2, 9.4, 7.0, 6.8; IR (neat): ν=3081, 3004, 1946, 1597, 1492, 1458, 1423, 1251, 1047, 1020 cm−1; MS (70 eV, EI) m/z (%): 156 (M+, 86.83), 115 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.9 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1a (191.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2d (118.8 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ad (111.0 mg, 54% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.35-7.24 (m, 8H, Ar—H), 7.24-7.15 (m, 2H, Ar—H), 6.17 (dt, J1=5.5 Hz, J2=2.8 Hz, 1H, ═CH), 5.72 (q, J=7.1 Hz, 1H, ═CH), 3.47 (dd, J1=7.4 Hz, J2=2.2 Hz, 2H, CH2); 13C NMR (100 MHz, CDCl3): δ=205.7, 140.0, 134.6, 128.5, 128.4, 126.8, 126.7, 126.3, 94.9, 94.4, 35.5; IR (neat): ν=3028, 1948, 1599, 1493, 1454, 1072, 1028 cm−1; MS (70 eV, EI) m/z (%): 206 (M+, 100).
The operation is the same as Example 1. 5 Å molecular sieves (250.1 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1a (191.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and the terminal alkyne 2e (102.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ae (118.8 mg, 62% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.43-7.26 (m, 8H, Ar—H), 7.26-7.16 (m, 2H, Ar—H), 6.59 (s, 2H, ═CH×2); 13C NMR (100 MHz, CDCl3): δ=207.7, 133.5, 128.7, 127.3, 127.0, 98.4; IR (neat): ν=3027, 1935, 1596, 1491, 1449, 1254, 1071, 1027 cm−1; MS (70 eV, EI) m/z (%): 192 (M+, 100).
The operation is the same as Example 1. 5 Å molecular sieves (250.6 mg), Au3d (43.2 mg, 0.05 mmol), aldehyde 1b (223.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.9 mg, 1.2 mmol) and terminal alkyne 2a (110.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ba (185.6 mg, 85% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.29-7.17 (m, 2H, Ar—H), 7.03-6.91 (m, 2H, Ar—H), 6.08 (dt, J1=6.1 Hz, J2=3.1 Hz, 1H, ═CH), 5.56 (q, J=6.7 Hz, 1H, ═CH), 2.17 (qd, J1=7.1 Hz, J2=3.0 Hz, 2H, CH2), 1.53-1.41 (m, 2H, CH2), 1.41-1.18 (m, 6H, CH2×3), 0.88 (t, J=6.6 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=204.9 (d, J=2.5 Hz), 161.7 (d, J=244.5 Hz), 131.1 (d, J=3.2 Hz), 127.9 (d, J=8.1 Hz), 115.4 (d, J=21.4 Hz), 95.3, 93.6, 31.6, 29.1, 28.9, 28.8, 22.7, 14.0; 19F NMR (376 MHz, CDCl3): δ=−116.5; IR (neat): ν=2925, 2855, 1948, 1602, 1506, 1463, 1226, 1154 cm−1; MS (70 eV, EI) m/z (%): 218 (M+, 2.01), 148 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.6 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1c (253.3 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2a (109.6 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ca (190.2 mg, 81% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.25 (d, J=8.8 Hz, 2H, Ar—H), 7.20 (d, J=8.4 Hz, 2H, Ar—H), 6.07 (dt, J1=6.4 Hz, J2=3.1 Hz, 1H, ═CH), 5.57 (q, J=6.7 Hz, 1H, ═CH), 2.12 (qd, J1=7.1 Hz, J2=3.0 Hz, 2H, CH2), 1.53-1.41 (m, 2H, CH2), 1.41-1.18 (m, 6H, CH2×3), 0.88 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.2, 133.7, 132.1, 128.6, 127.7, 95.4, 93.7, 31.6, 29.0, 28.8, 28.6, 22.6, 14.0; IR (neat): ν=2924, 2854, 1949, 1490, 1462, 1090, 1012 cm−1; MS (70 eV, EI) m/z (%): 234 (M+(35Cl), 1.40), 236 (M+(37Cl), 0.62), 129 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.2 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1d (333.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2a (110.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4da (215.8 mg, 77% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.40 (d, J=8.4 Hz, 2H, Ar—H), 7.14 (d, J=8.0 Hz, 2H, Ar—H), 6.11-6.01 (m, 1H, ═CH), 5.56 (q, J=6.7 Hz, 1H, ═CH), 2.12 (qd, J1=7.1 Hz, J1=2.4 Hz, 2H, CH2), 1.52-1.41 (m, 2H, CH2), 1.41-1.18 (m, 6H, CH2×3), 0.88 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.2, 134.2, 131.5, 128.0, 120.1, 95.5, 93.8, 31.6, 29.0, 28.8, 28.6, 22.6, 14.0; IR (neat): ν=2924, 2853, 1948, 1486, 1463, 1382, 1069, 1009 cm−1; MS (70 eV, EI) m/z (%): 278 (M+(79Br), 1.71), 280 (M+(81Br), 1.61), 129 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1e (417.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2a (110.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ea (228.3 mg, 70% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.60 (d, J=8.8 Hz, 2H, Ar—H), 7.02 (d, J=8.0 Hz, 2H, Ar—H), 6.04 (dt, J1=6.1 Hz, J2=3.0 Hz, 1H, ═CH), 5.56 (q, J=6.8 Hz, 1H, ═CH), 2.12 (qd, J1=7.1 Hz, J2=2.8 Hz, 2H, CH2), 1.52-1.40 (m, 2H, CH2), 1.40-1.18 (m, 6H, CH2×3), 0.88 (t, J=6.6 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.3, 137.5, 134.8, 128.3, 95.5, 93.9, 91.4, 31.6, 29.0, 28.8, 28.6, 22.6, 14.1; IR (neat): ν=2923, 2852, 1948, 1483, 1462, 1381, 1058, 1004 cm−1; MS (70 eV, EI) m/z (%): 326 (M+, 2.26), 129 (100); HRMS Calcd. for C15H19I (M+): 326.0526, found 326.0529.
The operation is the same as Example 1. 5 Å molecular sieves (250.4 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1f (245.7 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2a (110.4 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4fa (180.1 mg, 78% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.21 (d, J=8.4 Hz, 2H, Ar—H), 6.84 (d, J=8.4 Hz, 2H, Ar—H), 6.08 (dt, J1=6.1 Hz, J2=3.0 Hz, 1H, ═CH), 5.53 (q, J=6.7 Hz, 1H, ═CH), 3.80 (s, 3H, OCH3), 2.11 (qd, J1=7.1 Hz, J2=3.1 Hz, 2H, CH2), 1.52-1.41 (m, 2H, CH2), 1.41-1.18 (m, 6H, CH2×3), 0.88 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=204.4, 158.5, 127.5, 127.4, 114.0, 95.0, 93.9, 55.2, 31.6, 29.1, 28.9, 28.8, 22.6, 14.0; IR (neat): ν=2925, 2854, 1947, 1607, 1510, 1462, 1300, 1243, 1170, 1035 cm−1; MS (70 eV, EI) m/z (%): 230 (M+, 20.68), 160 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.3 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1g (237.0 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.3 mg, 1.2 mmol) and terminal alkyne 2a (112.6 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ga (175.2 mg, 78% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.59-7.53 (m, 2H, Ar—H), 7.38-7.33 (m, 2H, Ar—H), 6.13 (dt, J1=6.3 Hz, J2=3.1 Hz, 1H, ═CH), 5.66 (q, J=6.7 Hz, 1H, ═CH), 2.15 (qd, J1=7.1 Hz, J2=3.0 Hz, 2H, CH2), 1.53-1.41 (m, 2H, CH2), 1.41-1.20 (m, 6H, CH2×3), 0.88 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=206.5, 140.4, 132.2, 126.9, 119.1, 109.6, 96.0, 93.9, 31.5, 28.9, 28.8, 28.3, 22.5, 14.0; IR (neat): ν=2925, 2854, 2225, 1946, 1604, 1503, 1462, 1394, 1173 cm−1; MS (70 eV, EI) m/z (%): 225 (M+, 3.53), 129 (100); HRMS Calcd. for C16H19N (M+): 225.1512, found 225.1515.
The operation is the same as Example 1. 5 Å molecular sieves (250.8 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1h (301.8 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2a (112.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ha (199.1 mg, 77% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=100/1)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.96 (d, J 8.0 Hz, 2H, Ar—H), 7.33 (d, J 8.0 Hz, 2H, Ar—H), 6.18-6.11 (m, 1H, ═CH), 5.61 (q, J=6.7 Hz, 1H, ═CH), 3.90 (s, 3H, OCH3), 2.14 (qd, J1=7.1 Hz, J2=2.7 Hz, 2H, CH2), 1.53-1.41 (m, 2H, CH2), 1.41-1.20 (m, 6H, CH2×3), 0.88 (t, J=6.6 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=206.3, 166.9, 140.3, 129.8, 128.1, 126.3, 95.5, 94.2, 51.9, 31.6, 29.0, 28.8, 28.5, 22.6, 14.0; IR (neat): ν=2925, 2854, 1947, 1718, 1606, 1434, 1272, 1173, 1105 cm−1; MS (70 eV, EI) m/z (%): 258 (M+, 1.27), 129 (100); HRMS Calcd. for C17H22O2(M+): 258.1614, found 258.1613.
The operation is the same as Example 1. 5 Å molecular sieves (250.5 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1i (313.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2a (110.5 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ia (215.2 mg, 80% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.50 (d, J=8.4 Hz, 2H, Ar—H), 7.34 (d, J=8.0 Hz, 2H, Ar—H), 6.12 (dt, J1=6.3 Hz, J2=3.1 Hz, 1H, ═CH), 5.60 (q, J=6.7 Hz, 1H, ═CH), 2.13 (qd, J1=7.1 Hz, J2=3.0 Hz, 2H, CH2), 1.53-1.41 (m, 2H, CH2), 1.40-1.21 (m, 6H, CH2×3), 0.87 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=206.2, 139.2, 128.6 (q, J=32.2 Hz), 126.6, 125.4 (q, J=3.8 Hz), 124.4 (q, J=269.9 Hz), 95.7, 93.8, 31.7, 29.1, 28.9, 28.5, 22.7, 14.0; 19F NMR (376 MHz, CDCl3) δ=−62.9; IR (neat): ν=2927, 2856, 1950, 1615, 1439, 1322, 1163, 1121, 1064 cm−1; MS (70 eV, EI) m/z (%): 268 (M+, 1.13), 129 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.1 mg), Au3d (43.7 mg, 0.05 mmol), aldehyde 1j (272.0 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2f (209.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4jf (276.2 mg, 80% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=10/1)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=8.16 (d, J=9.2 Hz, 2H, Ar—H), 7.40 (d, J=8.8 Hz, 2H, Ar—H), 6.27 (dd, J=6.6 Hz, J2=3.0 Hz, 1H, ═CH), 5.71 (t, J=6.0 Hz, 1H, ═CH), 4.27-3.84 (br, 2H, CH2), 2.82 (t, J=12.2 Hz, 2H, CH2), 2.42-2.28 (m, 1H, CH), 1.88-1.73 (m, 2H, CH2), 1.45 (s, 9H, OC(CH3)3), 1.43-1.29 (m, 2H, CH2); 13C NMR (100 MHz, CDCl3): δ=206.1, 154.6, 146.3, 142.0, 126.8, 123.9, 100.2, 95.1, 79.4, 43.4, 35.4, 31.7, 28.3; IR (neat): ν=2976, 2932, 2852, 1946, 1680, 1595, 1515, 1421, 1338, 1229, 1164, 1110 cm−1; MS (ESI) m/z (%): 367 (M+Na+); HRMS Calcd. for C19H24O4N2Na (M+Na+): 367.1628, found 367.1623.
The operation is the same as Example 1. 5 Å molecular sieves (250.2 mg), Au3d (43.1 mg, 0.05 mmol), aldehyde 1k (417.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2g (80.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4 kg (249.2 mg, 84% yield) (purified by flash column chromatography (eluent: petroleum ether/ethyl acetate=200/1)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.73 (d, J=8.0 Hz, 2H, Ar—H), 7.28 (d, J=8.0 Hz, 2H, Ar—H), 6.23-6.06 (m, 1H, ═CH), 5.94-5.77 (m, 1H, ═CH), 5.67-5.50 (m, 1H, ═CH), 5.05 (dd, J1=17.0 Hz, J2=1.4 Hz, 1H, one proton of ═CH2), 5.00 (d, J=10.0 Hz, 1H, one proton of ═CH2), 2.32-2.15 (m, 4H, CH2×2), 1.34 (s, 12H, CH3×4); 13C NMR (100 MHz, CDCl3): δ=205.7, 137.9, 137.8, 135.0, 125.9, 115.2, 95.1, 94.4, 83.6, 33.1, 28.0, 24.81, 24.79; IR (neat): ν=2977, 2926, 1947, 1607, 1356, 1320, 1142, 1086 cm−1; MS (FI) m/z (%): 296 (M+(11B)); HRMS Calcd. for C19H25O210B (M+): 295.1978, found 295.1977.
The operation is the same as Example 1. 5 Å molecular sieves (250.6 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1k (417.6 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.9 mg, 1.2 mmol) and terminal alkyne 2h (116.4 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4kh (243.2 mg, 73% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=80/1)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.74 (d, J=7.6 Hz, 2H, Ar—H), 7.27 (d, J=8.0 Hz, 2H, Ar—H), 6.15 (dt, J=6.3 Hz, J2=3.1 Hz, 1H, ═CH), 5.57 (q, J=6.7 Hz, 1H, ═CH), 3.53 (t, J=6.6 Hz, 2H, CH2), 2.17 (qd, J1=6.9 Hz, J2=2.8 Hz, 2H, CH2), 1.91-1.79 (m, 2H, CH2), 1.70-1.56 (m, 2H, CH2), 1.34 (s, 12H, CH3×4); 13C NMR (100 MHz, CDCl3): δ=205.7, 137.7, 135.0, 125.8, 95.1, 94.3, 83.6, 44.6, 31.9, 27.7, 26.1, 24.8, 24.7; IR (neat): ν=2977, 2935, 1947, 1607, 1356, 1319, 1142, 1086 cm−1; MS (FI) m/z (%): 332 (M+(11B, 35Cl)); HRMS Calcd. for C19H26O210B35Cl (M+): 331.1745, found 331.1751.
The operation is the same as Example 1. 5 Å molecular sieves (250.5 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1k (418.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.7 mg, 1.2 mmol) and terminal alkyne 2i (133.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ki (199.9 mg, 57% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=200/1)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.74 (d, J=8.0 Hz, 2H, Ar—H), 7.31 (d, J=7.6 Hz, 2H, Ar—H), 6.22 (dt, J=6.1 Hz, J2=3.0 Hz, 1H, ═CH), 5.62 (q, J=6.7 Hz, 1H, ═CH), 3.48 (t, J=6.8 Hz, 2H, CH2), 2.78-2.62 (m, 2H, CH2), 1.34 (s, 12H, CH3×4); 13C NMR (100 MHz, CDCl3): δ=206.2, 137.0, 135.0, 126.1, 95.9, 92.5, 83.6, 32.0, 31.6, 24.81, 24.78; IR (neat): ν=2977, 1949, 1607, 1393, 1356, 1320, 1269, 1142, 1085 cm−1; MS (70 eV, EI) m/z (%): 347 (M+(10B, 79Br), 5.98), 348 (M+(10B, 79Br), 22.06), 349 (M+(10B, 81Br), 9.26), 350 (M+(11B, 81Br), 20.95), 169 (100); HRMS Calcd. for C17H22O210B79Br (M+): 347.0927, found 347.0931.
The operation is the same as Example 1. 5 Å molecular sieves (250.6 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1k (417.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.4 mg, 1.2 mmol) and terminal alkyne 2j (226.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4kj (355.3 mg, 80% yield) (purified by flash column chromatography (eluent:petroleum ether (200 mL); petroleum ether/ethyl acetate=80/1 (405 mL))): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.73 (d, J=8.0 Hz, 2H, Ar—H), 7.28 (d, J=8.0 Hz, 2H, Ar—H), 6.12 (dt, J1=6.3 Hz, J2=3.1 Hz, 1H, ═CH), 5.58 (q, J=6.7 Hz, 1H, ═CH), 3.58 (t, J=6.6 Hz, 2H, OCH2), 2.14 (qd, J1=7.0 Hz, J2=2.9 Hz, 2H, CH2), 1.57-1.44 (m, 4H, CH2×2), 1.44-1.36 (m, 2H, CH2), 1.34 (s, 12H, CH3×4), 0.89 (s, 9H, C(CH3)3), 0.04 (s, 6H, CH3×2); 13C NMR (100 MHz, CDCl3): δ=205.7, 138.1, 135.0, 125.9, 95.0, 94.8, 83.6, 63.2, 32.6, 28.9, 28.6, 26.0, 25.4, 24.9, 24.8, 18.4, −5.3; IR (neat): ν=2931, 2857, 1997, 1608, 1358, 1144, 1088 cm−1; MS (FI) m/z (%): 442 (M+(11B)); HRMS Calcd. for C26H43O3Si10B (M+): 441.3105, found 441.3108.
The operation is the same as Example 1. 5 Å molecular sieves (250.1 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1k (417.7 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.9 mg, 1.2 mmol) and terminal alkyne 2k (112.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4kk (258.5 mg, 96% purity, 76% yield) (purified by flash column chromatography (Eluent: petroleum ether/ethyl acetate=10/1)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.73 (d, J=7.6 Hz, 2H, Ar—H), 7.28 (d, J=8.0 Hz, 2H, Ar—H), 6.13 (dt, J1=6.4 Hz, J2=3.1 Hz, 1H, ═CH), 5.58 (q, J=6.5 Hz, 1H, ═CH), 3.62 (t, J=6.6 Hz, 2H, CH2), 2.15 (qd, J1=6.9 Hz, J2=3.0 Hz, 2H, CH2), 1.80-1.62 (brs, 1H, OH), 1.62-1.47 (m, 4H, CH2×2), 1.47-1.38 (m, 2H, CH2), 1.34 (s, 12H, CH3×4); 13C NMR (100 MHz, CDCl3): δ=205.6, 138.0, 134.9, 125.8, 94.8, 94.7, 83.6, 62.6, 32.3, 28.7, 28.4, 25.2, 24.73, 24.70; IR (neat): ν=3354, 2977, 2931, 2858, 1947, 1607, 1356, 1319, 1142, 1086 cm−1; MS (FI) m/z (%): 328 (M+(11B)); HRMS Calcd. for C20H29O310B (M+): 327.2241, found 327.2245.
The operation is the same as Example 1. 5 Å molecular sieves (250.1 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1k (417.9 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.7 mg, 1.2 mmol) and terminal alkyne 21 (107.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4kl (262.8 mg, 81% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=40/1 (410 mL); petroleum ether/ethyl acetate=20/1 (420 mL)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.74 (d, J=8.0 Hz, 2H, Ar—H), 7.27 (d, J=8.0 Hz, 2H, Ar—H), 6.17 (dt, J1=6.1 Hz, J2=3.0 Hz, 1H, ═CH), 5.57 (q, J=6.5 Hz, 1H, ═CH), 2.33 (t, J=7.0 Hz, 2H, CH2), 2.18 (qd, J1=7.0 Hz, J2=3.0 Hz, 2H, CH2), 1.80-1.69 (m, 2H, CH2), 1.69-1.58 (m, 2H, CH2), 1.34 (s, 12H, CH3×4); 13C NMR (100 MHz, CDCl3): δ=205.7, 137.6, 135.0, 125.8, 119.5, 95.3, 94.0, 83.7, 27.7, 27.6, 24.81, 24.78, 24.73, 16.9; IR (neat): ν=2975, 2937, 2896, 1949, 1605, 1355, 1323, 1147, 1089 cm−1; MS (FI) m/z (%): 323 (M+(11B)); HRMS Calcd. for C20H26O2N10B (M+): 322.2087, found 322.2081.
The operation is the same as Example 1. 5 Å molecular sieves (250.1 mg), Au3d (43.7 mg, 0.05 mmol), aldehyde 1k (418.0 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2m (126.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4 km (240.6 mg, 70% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=80/1 (405 mL); petroleum ether/ethyl acetate=40/1 (820 mL)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.73 (d, J=8.0 Hz, 2H, Ar—H), 7.27 (d, J=9.2 Hz, 2H, Ar—H), 6.16 (dt, J1=6.1 Hz, J2=3.0 Hz, 1H, ═CH), 5.57 (q, J=6.7 Hz, 1H, ═CH), 3.66 (s, 3H, OCH3), 2.39 (t, J=7.6 Hz, 2H, CH2), 2.25-2.12 (m, 2H, CH2), 1.89-1.75 (m, 2H, CH2), 1.34 (s, 12H, CH3×4); 13C NMR (100 MHz, CDCl3): δ=205.8, 173.8, 137.7, 135.0, 125.9, 95.2, 94.1, 83.6, 51.4, 33.3, 27.9, 24.80, 24.77, 24.1; IR (neat): ν=2977, 1947, 1737, 1607, 1356, 1142, 1086 cm−1; MS (FI) m/z (%): 342 (M+(11B)); HRMS Calcd. for C20H27O410B (M+): 341.2033, found 341.2039.
The operation is the same as Example 1. 5 Å molecular sieves (12.5025 g), Au3d (1.0851 g, 1.25 mmol), aldehyde 1k (20.8894 g, 90 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (8.8317 g, 60 mmol) and terminal alkyne 2m (6.3093 g, 50 mmol) were reacted in 2,2,2-trifluoroethanol (50 mL) to afford an allene product 4 km (10.9863 g, 64% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=40/1)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.73 (d, J=8.0 Hz, 2H, Ar—H), 7.27 (d, J=9.2 Hz, 2H, Ar—H), 6.16 (dt, J=6.1 Hz, J2=3.0 Hz, 1H, ═CH), 5.57 (q, J=6.7 Hz, 1H, ═CH), 3.66 (s, 3H, OCH3), 2.39 (t, J=7.4 Hz, 2H, CH2), 2.18 (qd, J1=6.9 Hz, J2=2.9 Hz, 2H, CH2), 1.89-1.74 (m, 2H, CH2), 1.34 (s, 12H, CH3×4).
The operation is the same as Example 1. 5 Å molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 11 (263.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (177.1 mg, 1.2 mmol) and terminal alkyne 2n (96.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ln (208.9 mg, 93% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.59 (d, J=2.4 Hz, 1H, Ar—H), 7.48 (s, 1H, Ar—H), 7.42 (d, J=8.8 Hz, 1H, Ar—H), 7.31-7.22 (m, 1H, Ar—H), 6.75-6.68 (m, 1H, Ar—H), 6.22 (dt, J1=6.3 Hz, J2=3.1 Hz, 1H, ═CH), 5.58 (q, J=6.7 Hz, 1H, ═CH), 2.14 (qd, J1=7.1 Hz, J2=2.9 Hz, 2H, CH2), 1.54-1.43 (m, 2H, CH2), 1.42-1.23 (m, 4H, CH2×2), 0.89 (t, J=7.0 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=204.7, 154.1, 145.2, 129.9, 127.8, 123.1, 118.9, 111.3, 106.4, 95.1, 94.6, 31.4, 28.8, 22.4, 14.0; IR (neat): ν=2925, 2855, 1948, 1466, 1452, 1262, 1192, 1111, 1031 cm−1; MS (70 eV, EI) m/z (%): 226 (M+, 12.48), 170 (100); HRMS Calcd. for C16H18O (M+): 226.1352, found 226.1356.
The operation is the same as Example 1. 5 Å molecular sieves (250.4 mg), Au3d (43.1 mg, 0.05 mmol), aldehyde 1m (193.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2n (96.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4mn (152.3 mg, 81% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=20/1)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=8.51 (d, J=1.6 Hz, 1H, Ar—H), 8.41 (dd, J1=4.8 Hz, J2=1.2 Hz, 1H, Ar—H), 7.58 (dt, J1=7.6 Hz, J2=1.6 Hz, 1H, Ar—H), 7.21 (dd, J1=7.6 Hz, J2=4.8 Hz, 1H, Ar—H), 6.10 (dt, J1=6.4 Hz, J2=3.2 Hz, 1H, ═CH), 5.63 (q, J=6.7 Hz, 1H, ═CH), 2.14 (qd, J1=7.2 Hz, J2=3.1 Hz, 2H, CH2), 1.57-1.41 (m, 2H, CH2), 1.40-1.22 (m, 4H, CH2×2), 0.89 (t, J=7.0 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.4, 147.9, 147.5, 133.1, 130.9, 123.2, 95.6, 91.2, 31.2, 28.6, 28.3, 22.3, 13.9; IR (neat): ν=2925, 2855, 1949, 1570, 1480, 1444, 1390, 1180, 1120, 1023 cm−1; MS (70 eV, EI) m/z (%): 187 (M+, 1.42), 130 (100); HRMS Calcd. for C13H17N (M+): 187.1356, found 187.1359.
The operation is the same as Example 1. 5 Å molecular sieves (250.2 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde in (173.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2n (96.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4nn (63.8 mg, 36% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.38-7.31 (m, 1H, Ar—H), 6.37 (dd, J1=3.2 Hz, J2=2.0 Hz, 1H, Ar—H), 6.18 (d, J=3.2 Hz, 1H, Ar—H), 6.10 (dt, J1=6.3 Hz, J2=3.1 Hz, 1H, ═CH), 5.60 (q, J=6.8 Hz, 1H, ═CH), 2.12 (qd, J1=7.1 Hz, J2=3.0 Hz, 2H, CH2), 1.53-1.42 (m, 2H, CH2), 1.40-1.22 (m, 4H, CH2×2), 0.89 (t, J=7.0 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=204.4, 149.0, 141.7, 111.3, 106.5, 95.6, 85.3, 31.3, 28.8, 28.5, 22.4, 14.0; IR (neat): ν=2926, 2856, 1950, 1462, 1249, 1174, 1150, 1076, 1010 cm−1; MS (70 eV, EI) m/z (%): 176 (M+, 11.56), 120 (100); HRMS Calcd. for C12H16O (M+): 176.1196, found 176.1200.
The operation is the same as Example 1. 5 Å molecular sieves (250.5 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde to (201.7 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2n (96.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4on (154.0 mg, 80% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.24 (dd, J1=5.2 Hz, J2=2.8 Hz, 1H, Ar—H), 7.06 (d, J=4.8 Hz, 1H, Ar—H), 7.03 (d, J=2.8 Hz, 1H, Ar—H), 6.18 (dt, J1=6.1 Hz, J2=3.1 Hz, 1H, ═CH), 5.49 (q, J=6.5 Hz, 1H, ═CH), 2.10 (qd, J1=7.1 Hz, J2=3.0 Hz, 2H, CH2), 1.52-1.42 (m, 2H, CH2), 1.39-1.24 (m, 4H, CH2×2), 0.89 (t, J=7.0 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.4, 136.5, 126.2, 125.6, 120.0, 94.2, 89.1, 31.3, 28.78, 28.77, 22.4, 14.0; IR (neat): ν=2924, 2854, 1950, 1462, 1378, 1261, 1232, 1077 cm−1; MS (70 eV, EI) m/z (%): 192 (M+, 5.72), 135 (100); HRMS Calcd. for C12H16S (M+): 192.0967, found 192.0966.
The operation is the same as Example 1. 5 Å molecular sieves (250.6 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1p (263.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2o (108.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4po (203.0 mg, 85% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=4/1)): white solid; m.p. 152.0-152.9° C. (recrystallized from ethyl acetate); 1H NMR (400 MHz, CDCl3): δ=10.80-10.04 (brs, 1H, NH), 8.03 (s, 1H, Ar—H), 7.59 (s, 1H, Ar—H), 7.43 (s, 2H, Ar—H), 6.28 (dd, J1=6.4 Hz, J2=2.8 Hz, 1H, ═CH), 5.60 (t, J=6.0 Hz, 1H, ═CH), 2.23-2.04 (m, 1H, CH), 1.94-1.82 (m, 2H), 1.82-1.68 (m, 2H), 1.68-1.57 (m, 1H), 1.40-1.08 (m, 5H); 13C NMR (100 MHz, CDCl3): δ=203.7, 139.4, 134.7, 128.4, 126.0, 123.7, 118.1, 109.9, 101.2, 95.5, 37.7, 33.2, 33.1, 26.1, 26.02, 26.01; IR (neat): ν=3139, 2918, 2848, 1946, 1623, 1506, 1442, 1341, 1307, 1081 cm−1; MS (ESI) m/z (%): 239 (M+H+); Anal. Calcd. for C16H18N2: C 80.63, H, 7.61, N 11.75, found C 80.49, H 7.69, N 11.72.
The operation is the same as Example 1. 5 Å molecular sieves (250.2 mg), Au3d (43.1 mg, 0.05 mmol), aldehyde 1q (261.0 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.4 mg, 1.2 mmol) and terminal alkyne 2o (107.8 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4qo (133.6 mg, 57% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=40/1)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=8.22-7.85 (brs, 1H, NH), 7.52 (s, 1H, Ar—H), 7.29 (d, J=8.4 Hz, 1H, Ar—H), 7.22 (t, J=7.6 Hz, 1H, Ar—H) 7.13 (s, 1H, Ar—H), 6.49 (s, 1H, Ar—H), 6.28 (dd, J1=6.0 Hz, J2=2.8 Hz, 1H, ═CH), 5.56 (t, J=6.2 Hz, 1H, ═CH), 2.22-2.05 (m, 1H, CH), 1.95-1.80 (m, 2H), 1.80-1.68 (m, 2H), 1.68-1.58 (m, 1H), 1.38-1.08 (m, 5H); 13C NMR (100 MHz, CDCl3): δ=203.3, 134.9, 128.1, 126.7, 124.5, 120.9, 118.5, 111.2, 102.4, 100.8, 96.1, 37.7, 33.2, 33.1, 26.1, 26.03, 26.02; IR (neat): ν=3410, 2921, 2848, 1945, 1447, 1415, 1319, 1285, 1091 cm−1; MS (ESI) m/z (%): 238 (M+H+); HRMS Calcd. for C17H20N (M+H+): 238.1590, found 238.1588.
The operation is the same as Example 1. 5 Å molecular sieves (250.4 mg), Au3d (43.7 mg, 0.05 mmol), aldehyde 1r (281.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.4 mg, 1.2 mmol) and terminal alkyne 2g (80.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4rg (145.7 mg, 66% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.82-7.70 (m, 3H, Ar—H), 7.64 (s, 1H, Ar—H), 7.53-7.47 (m, 1H, Ar—H), 7.47-7.36 (m, 2H, Ar—H), 6.37-6.26 (m, 1H, ═CH), 5.96-5.78 (m, 1H, ═CH), 5.65 (q, J=6.1 Hz, 1H, ═CH), 5.08 (d, J=17.6 Hz, 1H, one proton of ═CH2), 5.02 (d, J=10.0 Hz, 1H, one proton of ═CH2), 2.36-2.17 (m, 4H, CH2×2); 13C NMR (100 MHz, CDCl3): δ=205.7, 137.8, 133.7, 132.5, 132.4, 128.1, 127.63, 127.58, 126.1, 125.4, 125.3, 124.6, 115.2, 95.3, 94.6, 33.1, 28.1; IR (neat): ν=3054, 2976, 2909, 2843, 1945, 1639, 1597, 1507, 1435, 1264 cm−1; MS (70 eV, EI) m/z (%): 220 (M+, 91.99), 178 (100); HRMS Calcd. for C17H16 (M+): 220.1247, found 220.1248.
The operation is the same as Example 1. 5 Å molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde is (371.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2g (80.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4sg (139.9 mg, 52% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=8.74-8.66 (m, 1H, Ar—H), 8.62 (d, J=8.0 Hz, 1H, Ar—H), 8.36-8.27 (m, 1H, Ar—H), 7.87-7.81 (m, 1H, Ar—H), 7.78 (s, 1H, Ar—H), 7.69-7.48 (m, 4H, Ar—H), 6.87-6.78 (m, 1H, ═CH), 5.96-5.80 (m, 1H, ═CH), 5.64 (q, J=6.5 Hz, 1H, ═CH), 5.08 (d, J=17.2 Hz, 1H, one proton of ═CH2), 5.01 (d, J=10.0 Hz, 1H, one proton of ═CH2), 2.39-2.22 (m, 4H, CH2×2); 13C NMR (100 MHz, CDCl3): δ=206.7, 137.9, 131.8, 130.7, 130.2, 129.8, 129.6, 128.3, 126.7, 126.5, 126.34, 126.28, 125.9, 124.4, 123.1, 122.5, 115.3, 93.2, 91.7, 33.2, 28.2; IR (neat): ν=3073, 2973, 2909, 2844, 1946, 1639, 1494, 1428, 1243, 1114 cm−1; MS (70 eV, EI) m/z (%): 270 (M+, 100); HRMS Calcd. for C21H18 (M+): 270.1403, found 270.1408.
The operation is the same as Example 1. 5 Å molecular sieves (250.2 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde it (414.6 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2g (79.8 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4tg (151.6 mg, 52% yield) (purified by flash column chromatography (eluent: petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=8.40 (d, J=9.2 Hz, 1H, Ar—H), 8.18-8.04 (m, 5H, Ar—H), 8.04-7.94 (m, 3H, Ar—H), 7.23-7.10 (m, 1H, ═CH), 5.98-5.83 (m, 1H, ═CH), 5.75 (q, J=6.1 Hz, 1H, ═CH), 5.10 (d, J=16.8 Hz, 1H, one proton of ═CH2), 5.03 (d, J=10.8 Hz, 1H, one proton of ═CH2), 2.43-2.24 (m, 4H, CH2×2); 13C NMR (100 MHz, CDCl3): δ=207.2, 137.9, 131.4, 130.8, 130.1, 128.5, 127.5, 127.4, 127.3, 126.9, 125.8, 125.2, 125.1, 125.04, 124.96, 124.9, 124.7, 122.7, 115.3, 94.0, 92.0, 33.3, 28.2; IR (neat): ν=3040, 2973, 2906, 2842, 1941, 1639, 1599, 1435, 1269, 1182 cm−1; MS (70 eV, EI) m/z (%): 294 (M+, 94.55), 253 (100); HRMS Calcd. for C23H18 (M+): 294.1403, found 294.1407.
The operation is the same as Example 1. 5 Å molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1u (256.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2a (110.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (5 mL) to afford an allene product 4ua (195.7 mg, 83% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=5.06 (quintet, J=4.8 Hz, 2H, ═CH×2), 2.07-1.86 (m, 4H, CH2×2), 1.48-1.13 (m, 20H, CH2×10), 0.96-0.77 (m, 6H, CH3×2); 13C NMR (150 MHz, CDCl3): δ=204.0, 90.87, 90.86, 32.0, 31.8, 29.6, 29.4, 29.32, 29.28, 29.2, 29.084, 29.078, 28.9, 22.75, 22.73, 14.09, 14.08; IR (neat): ν=2957, 2922, 2853, 1963, 1462, 1378, 1261 cm−1; MS (FI) m z (%): 236 (M+); HRMS Calcd. for C17H32 (M+): 236.2499, found 236.2500.
The operation is the same as Example 1. 5 Å molecular sieves (250.2 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1v (180.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2a (110.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (5 mL) to afford an allene product 4va (126.1 mg, 65% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=5.06 (quintet, J=4.8 Hz, 2H, ═CH×2), 2.06-1.86 (m, 4H, CH2×2), 1.48-1.16 (m, 14H, CH2×7), 0.97-0.74 (m, 6H, CH3×2); 13C NMR (100 MHz, CDCl3): δ=203.8, 90.9, 31.8, 31.4, 29.2, 29.04, 29.00, 28.9, 28.8, 22.7, 22.5, 14.08, 14.07; IR (neat): ν=2957, 2924, 2855, 1962, 1462, 1378, 1261, 1104, 1018 cm−1; MS (FI) m/z (%): 194 (M+); HRMS Calcd. for C14H26 (M+): 194.2029, found 194.2032.
The operation is the same as Example 1. 5 Å molecular sieves (250.2 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1w (155.3 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.2 mg, 1.2 mmol) and terminal alkyne 2a (110.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (5 mL) to afford an allene product 4wa (148.0 mg, 82% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=5.11-4.94 (m, 2H, ═CH×2), 2.02-1.92 (m, 2H, CH2), 1.92-1.78 (m, 2H, CH2), 1.72-1.58 (m, 1H, CH), 1.43-1.19 (m, 8H, CH2×4), 1.02-0.78 (m, 9H, CH3×3); 13C NMR (100 MHz, CDCl3): δ=204.5, 90.2, 89.4, 38.6, 31.7, 29.2, 29.0, 28.8, 28.5, 22.7, 22.3, 22.2, 14.1; IR (neat): ν=2956, 2925, 2855, 1963, 1464, 1381, 1366, 1261, 1105 cm−1; MS (FI) m z (%): 180 (M+); HRMS Calcd. for C13H24 (M+): 180.1873, found 180.1875.
The operation is the same as Example 1. 5 Å molecular sieves (250.1 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1x (202.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.3 mg, 1.2 mmol) and the terminal alkyne 2a (110.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (2 mL) to afford an allene product 4xa (161.2 mg, 78% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=5.20-4.97 (m, 2H, ═CH×2), 2.06-1.86 (m, 3H, CH2 and CH), 1.82-1.67 (m, 4H), 1.67-1.58 (m, 1H), 1.46-1.00 (m, 13H), 0.89 (t, J=6.8 Hz, 3H, CH3); 13C NMR (150 MHz, CDCl3): δ=202.7, 97.0, 91.8, 37.3, 33.18, 33.15, 31.7, 29.2, 29.1, 28.9, 26.2, 26.10, 26.09, 22.7, 14.1; IR (neat): ν=2922, 2851, 1960, 1448, 1260 cm−1; MS (70 eV, EI) m/z (%): 206 (M+, 2.43), 136 (100); HRMS Calcd. for C15H26 (M+): 206.2029, found 206.2032.
The operation is the same as Example 1. 5 Å molecular sieves (250.5 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1u (256.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.9 mg, 1.2 mmol) and terminal alkyne 2e (102.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (5 mL) to afford an allene product 4ue (161.1 mg, 70% yield, 99% purity) (purified by flash column chromatography (Eluant:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.36-7.26 (m, 4H, Ar—H), 7.22-7.13 (m, 1H, Ar—H), 6.12 (dt, J1=6.0 Hz, J2=2.9 Hz, 1H, ═CH), 5.56 (q, J=6.7 Hz, 1H, ═CH), 2.12 (qd, J1=7.1 Hz, J2=2.7 Hz, 2H, CH2), 1.53-1.41 (m, 2H, CH2), 1.41-1.11 (m, 10H, CH2×5), 0.88 (t, J=6.6 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.1, 135.1, 128.5, 126.54, 126.52, 95.1, 94.5, 31.8, 29.4, 29.3, 29.2, 29.1, 28.7, 22.7, 14.1; IR (neat): ν=2923, 2853, 1949, 1598, 1494, 1459 cm−1; MS (FI) m/z (%): 228 (M+); HRMS Calcd. for C17H24 (M+): 228.1873, found 228.1869.
The operation is the same as Example 1. 5 Å molecular sieves (250.0 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1x (202.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.3 mg, 1.2 mmol) and terminal alkyne 2e (102.0 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (2 mL) to afford an allene product 4xe (145.4 mg, 73% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.36-7.26 (m, 4H, Ar—H), 7.22-7.11 (m, 1H, Ar—H), 6.15 (dd, J1=6.2 Hz, J2=3.0 Hz, 1H, ═CH), 5.56 (t, J=6.2 Hz, 1H, ═CH), 2.18-2.04 (m, 1H, CH), 1.92-1.78 (m, 2H), 1.78-1.68 (m, 2H), 1.68-1.57 (m, 1H), 1.37-1.08 (m, 5H); 13C NMR (100 MHz, CDCl3): δ=204.0, 135.2, 128.5, 126.5, 126.4, 101.0, 95.4, 37.6, 33.15, 33.09, 26.09, 26.08, 26.02; IR (neat): ν=2921, 2849, 1946, 1597, 1493, 1446 cm−1; MS (70 eV, EI) m/z (%): 198 (M+, 5.19), 105 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.2 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1c (253.4 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.7 mg, 1.2 mmol) and terminal alkyne 2q (138.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4cq (200.1 mg, 76% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.28-7.22 (m, 2H, Ar—H), 7.22-7.16 (m, 2H, Ar—H), 6.07 (dt, J1=6.3 Hz, J2=3.1 Hz, 1H, ═CH), 5.57 (q, J=6.7 Hz, 1H, ═CH), 2.12 (qd, J1=7.1 Hz, J2=2.9 Hz, 2H, CH2), 1.53-1.41 (m, 2H, CH2), 1.41-1.14 (m, 10H, CH2×5), 0.87 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.2, 133.7, 132.1, 128.6, 127.7, 95.5, 93.7, 31.8, 29.4, 29.3, 29.2, 29.1, 28.6, 22.7, 14.1; IR (neat): ν=2923, 2853, 1949, 1490, 1463, 1090, 1013 cm−1; MS (70 eV, EI) m/z (%): 264 (M+(37Cl), 0.63), 262 (M+(35Cl), 2.02), 129 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.2 mg), Au3d (43.3 mg, 0.05 mmol), aldehyde 1d (333.5 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.6 mg, 1.2 mmol) and terminal alkyne 2q (138.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4dq (230.9 mg, 75% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.40 (d, J=8.4 Hz, 2H, Ar—H), 7.14 (d, J=8.4 Hz, 2H, Ar—H), 6.06 (dt, J1=6.3 Hz, J2=3.1 Hz, 1H, ═CH), 5.56 (q, J=6.5 Hz, 1H, ═CH), 2.12 (qd, J1=7.1 Hz, J2=2.9 Hz, 2H, CH2), 1.53-1.40 (m, 2H, CH2), 1.40-1.14 (m, 10H, CH2×5), 0.88 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.2, 134.2, 131.5, 128.0, 120.1, 95.5, 93.8, 31.8, 29.4, 29.3, 29.2, 29.1, 28.6, 22.7, 14.1; IR (neat): ν=2922, 2852, 1949, 1486, 1462, 1069, 1009 cm−1; MS (70 eV, EI) m/z (%): 308 (M+(81Br), 3.73), 306 (M+(79Br), 4.13), 210 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.6 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde 1i (313.2 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.3 mg, 1.2 mmol) and terminal alkyne 2b (166.3 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4ib (253.8 mg, 78% yield) (purified by flash column chromatography (eluent:petroleum ether)): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.53 (d, J=8.0 Hz, 2H, Ar—H), 7.37 (d, J=8.0 Hz, 2H, Ar—H), 6.14 (dt, J1=6.1 Hz, J2=3.0 Hz, 1H, ═CH), 5.63 (q, J=6.7 Hz, 1H, ═CH), 2.14 (qd, J1=7.1 Hz, J2=3.1 Hz, 2H, CH2), 1.53-1.41 (m, 2H, CH2), 1.41-1.12 (m, 14H, CH2×7), 0.88 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=206.2, 139.2, 128.6 (q, J=32.2 Hz), 126.6, 125.4 (q, J=3.8 Hz), 124.4 (q, J=269.6 Hz), 95.7, 93.8, 32.0, 29.71, 29.67, 29.5, 29.4, 29.2, 29.1, 28.5, 22.7, 14.1; 19F NMR (376 MHz, CDCl3) δ=−62.9; IR (neat): ν=2924, 2854, 1949, 1616, 1322, 1163, 1123, 1065 cm−1; MS (70 eV, EI) m/z (%): 324 (M+, 2.97), 198 (100).
The operation is the same as Example 1. 5 Å molecular sieves (250.3 mg), Au3d (43.4 mg, 0.05 mmol), aldehyde to (202.1 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.8 mg, 1.2 mmol) and terminal alkyne 2q (138.2 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4oq (201.5 mg, 86% yield) (purified by flash column chromatography (eluent:Petroleum ether)): Oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.27-7.21 (m, 1H, Ar—H), 7.06 (d, J=5.2 Hz, 1H, Ar—H), 7.04-6.99 (m, 1H, Ar—H), 6.18 (dt, J1=6.3 Hz, J2=3.0 Hz, 1H, ═CH), 5.48 (q, J=6.7 Hz, 1H, ═CH), 2.10 (qd, J1=7.0 Hz, J2=3.0 Hz, 2H, CH2), 1.52-1.42 (m, 2H, CH2), 1.40-1.12 (m, 10H, CH2×5), 0.88 (t, J=6.6 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3): δ=205.4, 136.5, 126.2, 125.6, 120.0, 94.2, 89.1, 31.8, 29.4, 29.3, 29.2, 29.1, 28.8, 22.7, 14.1; IR (neat): ν=2922, 2852, 1950, 1461, 1378, 1233 cm−1; MS (70 eV, EI) m/z (%): 234 (M+, 1.95), 135 (100).
Lithium hydroxide (18.0 mg, 0.75 mmol), allene 4 km (171.3 mg, 0.5 mmol), ethanol (2.5 mL) and water (2.5 mL) were added in sequence to a reaction flask. After the reaction bottle was put into an oil bath at 90° C. to react for 14 hours, water (2 mL) and aqueous hydrochloric acid (1 M, 2 mL) were added in sequence to the reaction bottle. The mixture was extracted with ether (4 mL×5). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to afford a product 6′ (151.9 mg, 93% purity, 86% yield): oily liquid; 1H NMR (400 MHz, CDCl3): δ=12.00-8.60 (br, 1H, CO2H), 7.74 (d, J=8.0 Hz, 2H, Ar—H), 7.27 (d, J=7.6 Hz, 2H, Ar—H), 6.17 (dt, J1=5.9 Hz, J2=2.9 Hz, 1H, ═CH), 5.57 (q, J=6.5 Hz, 1H, ═CH), 2.43 (t, J=7.4 Hz, 2H, CH2), 2.20 (qd, J1=7.1 Hz, J2=3.0 Hz, 2H, CH2), 1.90-1.75 (m, 2H, CH2), 1.34 (s, 12H, CH3×4); 13C NMR (100 MHz, CDCl3): δ=205.8, 179.8, 137.7, 135.0, 125.9, 95.3, 94.0, 83.7, 33.3, 27.8, 24.78, 24.75, 23.8; IR (neat): ν=2976, 1944, 1701, 1607, 1355, 1321, 1245, 1168, 1140, 1088 cm−1; MS (FI) m/z (%): 328 (M+(11B)); HRMS Calcd. for C19H25O410B (M+): 327.1877, found 327.1882.
Au(SIPr)Cl (6.2 mg, 0.01 mmol), AgOTs (2.9 mg, 0.01 mmol) and chloroform (2 mL) were added in sequence to a reaction flask. After stirring at room temperature for 15 minutes, 6′ (70.1 mg, 93% purity, 0.2 mmol) and chloroform (1 mL) were added in sequence. After stirring at room temperature for 36 hours, the reaction solution was filtered through a short silica gel column, and the filter cake was washed with ethyl acetate (30 mL), concentrated, purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=4/1) to afford a product (E)-6 (47.9 mg, 73% yield): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.77 (d, J=8.0 Hz, 2H, Ar—H), 7.39 (d, J=8.0 Hz, 2H, Ar—H), 6.68 (d, J=16.0 Hz, 1H, ═CH), 6.27 (dd, J1=15.8 Hz, J2=6.2 Hz, 1H, ═CH), 5.09-4.91 (m, 1H, OCH), 2.73-2.58 (m, 1H, one proton of CH2), 2.58-2.46 (m, 1H, one proton of CH2), 2.14-2.03 (m, 1H, one proton of CH2), 2.03-1.84 (m, 2H, one proton of CH2×2), 1.83-1.67 (m, 1H, one proton of CH2), 1.34 (s, 12H, CH3×4); 13C NMR (150 MHz, CDCl3): δ=171.0, 138.6, 135.1, 132.0, 128.0, 125.9, 83.8, 80.2, 29.6, 28.4, 24.824, 24.816, 18.3; IR (neat): ν=2977, 1731, 1607, 1357, 1233, 1142, 1087, 1033 cm−1; MS (FI) m/z (%): 328 (M+(11B); HRMS Calcd. for C19H25O410B (M+): 327.1877, found 327.1879.
Au(SIPr)Cl (31.3 mg, 0.05 mmol), AgOTf (12.8 mg, 0.05 mmol) and dioxane (1.25 mL) were added in sequence to a reaction flask. After stirring at room temperature for 15 minutes, 4 km (342.0 mg, 1.0 mmol) and water (36.0 mg, 2.0 mmol) were added in sequence. After stirring at room temperature for 24 hours, the reaction solution was filtered through a short silica gel column, and the filter cake was washed with diethyl ether (30 mL), concentrated, and purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=4/1) to afford a product (E)-7 (252.9 mg, 70% yield): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.76 (d, J=7.6 Hz, 2H, Ar—H), 7.37 (d, J=8.0 Hz, 2H, Ar—H), 6.59 (d, J=16.0 Hz, 1H, ═CH), 6.28 (dd, J1=15.6 Hz, J2=6.4 Hz, 1H, ═CH), 4.36-4.24 (m, 1H, CH), 3.67 (s, 3H, OCH3), 2.38 (t, J=7.2 Hz, 2H, CH2), 1.88-1.59 (m, 5H, CH2×2 and OH), 1.34 (s, 12H, CH3×4); 13C NMR (100 MHz, CDCl3): δ=174.0, 139.3, 135.0, 133.1, 130.3, 125.7, 83.7, 72.4, 51.5, 36.5, 33.7, 24.8, 20.8; IR (neat): ν=3466, 2978, 1732, 1608, 1357, 1142, 1087 cm−1; MS (FI) m/z (%): 360 (M+(11B); HRMS Calcd. for C20H29O510B (M+): 359.2139, found 359.2148.
Under an argon atmosphere, Pd(PPh3)2Cl2 (7.0 mg. 0.01 mmol), potassium carbonate (55.6 mg, 0.4 mmol), 4 km (68.4 mg, 0.2 mmol), 3-Bromoquinoline (62.7 mg, 0.3 mmol), freshly distilled dioxane (1 mL) and water (0.5 mL) were added in sequence to a dry reaction flask. The reaction flask was put into an oil bath at 80° C. for 5 hours. The reaction solution was filtered with a short silica gel column, and the filter cake was washed with ether, concentrated, and purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=3/1) to afford a product 8 (54.3 mg, 95% purity, 75% yield): oily liquid; 1H NMR (400 MHz, CDCl3): δ=9.19 (d, J=2.4 Hz, 1H, Ar—H), 8.30 (d, J=2.0 Hz, 1H, Ar—H), 8.13 (d, J=8.4 Hz, 1H, Ar—H), 7.88 (d, J=8.0 Hz, 1H, Ar—H), 7.76-7.69 (m, 1H, Ar—H), 7.67 (d, J=8.4 Hz, 2H, Ar—H), 7.62-7.54 (m, 1H, Ar—H), 7.44 (d, J=8.4 Hz, 2H, Ar—H), 6.23 (dt, J1=6.1 Hz, J2=3.0 Hz, 1H, ═CH), 5.63 (q, J=6.5 Hz, 1H, ═CH), 3.68 (s, 3H, OCH3), 2.42 (t, J=7.4 Hz, 2H, CH2), 2.29-2.13 (m, 2H, CH2), 1.92-1.80 (m, 2H, CH2); 13C NMR (100 MHz, CDCl3): δ=205.6, 173.8, 149.7, 147.2, 136.1, 134.8, 133.4, 132.7, 129.25, 129.16, 128.0, 127.9, 127.5, 127.3, 126.9, 94.6, 94.3, 51.5, 33.3, 28.0, 24.2; IR (neat): ν=2948, 1946, 1731, 1515, 1492, 1435, 1340, 1195, 1149 cm−1; MS (ESI) m z (%): 344 (M+H+); HRMS Calcd. for C23H22NO2 (M+H+): 344.1645, found 344.1644.
4 km (68.8 mg, 0.2 mmol), ammonium acetate (92.6 mg, 1.2 mmol), sodium periodate (257.1 mg, 1.2 mmol), acetone (2.4 mL) and distilled water (1.2 mL) were added in sequence to a reaction flask. After reacting at room temperature for 12 hours, the reaction solution was filtered with a short silica gel column, and the filter cake was washed with acetone (15 mL), concentrated, extracted with diethyl ether (4 mL×3), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, purified by flash column chromatography (eluent dichloromethane/methanol=80/1) to afford the corresponding boronic acid (47.9 mg).
Pd(PPh3)2Cl2 (3.9 mg, 5.56×10−3 mmol), potassium carbonate (76.5 mg, 0.554 mmol) and the above prepared boronic acid (47.9 mg, 0.184 mmol) were added in sequence to a dry reaction flask. After the reaction tube was plugged with a rubber stopper, inserted with a carbon monoxide balloon, connected to a vacuum pump, and replaced with the carbon monoxide three times under a carbon monoxide atmosphere. Then 1.1 mL of iodobenzene (41.4 mg, 0.203 mmol) in anisole solution was added. The reaction flask was placed in an oil bath at 80° C. and stirred for 6 hours. The reaction solution was filtered through a short silica gel column, and the filter cake was washed with diethyl ether (15 mL), concentrated, and purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=20/1) to afford a product 9 (37.3 mg, 58% yield): oily liquid; 1H NMR (400 MHz, CDCl3): δ=7.78 (t, J=8.4 Hz, 4H, Ar—H), 7.62-7.53 (m, 1H, Ar—H), 7.48 (t, J=7.6 Hz, 2H, Ar—H), 7.38 (d, J=8.4 Hz, 2H, Ar—H), 6.22 (dt, J1=6.3 Hz, J2=3.1 Hz, 1H, ═CH), 5.64 (q, J=6.5 Hz, 1H, ═CH), 3.67 (s, 3H, OCH3), 2.41 (t, J1=7.4 Hz, 2H, CH2), 2.21 (qd, J1=7.1 Hz, J2=2.9 Hz, 2H, CH2), 1.91-1.78 (m, 2H, CH2); 13C NMR (100 MHz, CDCl3): δ=206.5, 196.2, 173.8, 139.5, 137.8, 135.7, 132.2, 130.6, 129.9, 128.2, 126.3, 94.7, 94.6, 51.6, 33.3, 27.8, 24.1; IR (neat): ν=2949, 1945, 1732, 1652, 1599, 1435, 1306, 1275, 1174, 1148 cm−1; MS (ESI) m/z (%): 321 (M+H+); HRMS Calcd. for C21H21O3 (M+H+): 321.1485, found 321.1484.
The operation is the same as Example 1. 5 Å molecular sieves (250.4 mg), Au3d (43.5 mg, 0.05 mmol), aldehyde 1y (382.3 mg, 1.8 mmol), 1-methyl-1,2,3,4-tetrahydroisoquinoline 3f (176.5 mg, 1.2 mmol) and terminal alkyne 2p (202.1 mg, 1.0 mmol) were reacted in 2,2,2-trifluoroethanol (1 mL) to afford an allene product 4yp (255.2 mg, 64% yield) (purified by flash column chromatography (eluent:petroleum ether/ethyl acetate=40/1)): white solid; m.p. 71.0-72.2° C. (recrystallized from ether); 1H NMR (400 MHz, CDCl3): δ=7.89 (d, J=8.8 Hz, 2H, Ar—H), 7.45-7.34 (m, 4H, Ar—H), 7.34-7.27 (m, 1H, Ar—H), 7.20 (d, J=8.4 Hz, 2H, Ar—H), 6.89 (d, J=8.8 Hz, 4H, Ar—H), 6.15-6.06 (m, 1H, ═CH), 5.56 (q, J=6.5 Hz, 1H, ═CH), 5.03 (s, 2H, CH2), 3.85 (s, 3H, OCH3), 2.97 (t, J=7.4 Hz, 2H, CH2), 2.28-2.16 (m, 2H, CH2), 1.92 (quintet, J=7.1 Hz, 2H, CH2); 13C NMR (100 MHz, CDCl3): δ=204.6, 198.5, 163.2, 157.7, 136.8, 130.2, 130.0, 128.4, 127.8, 127.6, 127.31, 127.28, 115.0, 113.5, 94.30, 94.25, 69.9, 55.3, 37.3, 28.4, 23.5; IR (neat): ν=2897, 2840, 1943, 1670, 1602, 1577, 1509, 1231, 1167 cm−1; MS (70 eV, EI) m/z (%): 398 (M+, 3.73), 91 (100).
Those skilled in the art will understand that within the protection scope of the present invention, it is feasible to modify, add and replace the above-mentioned embodiments, and none of them exceeds the protection scope of the present invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 202111135110.5 | Sep 2021 | CN | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/CN2022/120980 | 9/23/2022 | WO |
