Patent Application
20210206702
This application claims the benefits of the Taiwan Patent Application Serial Number 109100028, filed on Jan. 2, 2020, the subject matter of which is incorporated herein by reference.
The present disclosure relates to a method of oxidative cleavage and, more particularly, to a method of oxidative cleavage for a compound with an unsaturated double bond under an aerobic condition to obtain a carbonyl compound.
Oxidative cleavage is one of the important reactions for a compound with an unsaturated double bond, such as olefins. Generally, olefins can be subjected to an oxidative cleavage reaction by (1) ozone; (2) high oxidation state metal oxides, such as potassium permanganate (KMnO4), or osmium tetroxide (OsO4); and (3) Pd/Cu catalysis.
However, due to the use of strong oxidants and peroxides for the reaction, the oxidative cleavage of olefins has the disadvantages of high cost and strict operating conditions, and it has difficulty in mass production. In addition, half of the oxidation products in the oxidative cleavage reaction is not the expected product in almost all cases, and it causes additional waste and environmental pollution.
Therefore, there is a strong and urgent demand to develop a method of oxidative cleavage for a compound with an unsaturated double bond to overcome the disadvantages of common oxidative cleavage and increase economic benefits.
In view of this, the present disclosure provides a method for oxidative cleavage of a compound with an unsaturated double bond. The method can be performed by using air or oxygen as an oxidant source under mild conditions, thereby overcoming the drawbacks of high cost or strict operating conditions with respect to conventional oxidative cleavage reactions. At the same time, the other half of the oxidation products are introduced with trifluoromethyl group, which greatly improves economic value.
The present disclosure provides a method for oxidative cleavage of a compound with an unsaturated double bond, comprising the steps of: (A) providing a compound (I) with an unsaturated double bond, a trifluoromethyl-containing reagent, and a catalyst;
wherein, R1 and R2 are each independently H, C1-20 alkyl, C3-20 cycloalkyl, C6-18 aryl, or C4-18 heteroaryl, or R1 and R2 are fused to be C6-18 aralkyl; R3 is H, C1-10 alkyl, C3-10 cycloalkyl, C6-10 aryl, or C4-10 heteroaryl, with the proviso that R1, R2 and R3 are not H at the same time; wherein the catalyst is represented by Formula (II):
M(O)mL1yL2z (II)
wherein, M is a metal selected from the group consisting of IVB, VB, VIB, and actinides; L1 and L2 are each a ligand; m and y are integers greater than or equal to 1; and z is an integer greater than or equal to 0;
(B) mixing the compound with an unsaturated double bond and the trifluoromethyl-containing reagent to perform an oxidative cleavage of the compound with the unsaturated double bond by using the catalyst in air or under oxygen atmosphere condition to obtain a compound represented by Formula (III):
The compound (1) with an unsaturated double bond according to the present disclosure may be an olefin compound. In the compound (I) with an unsaturated double bond, R1 and R2 are each independently H, C1-20 alkyl, C3-20 cycloalkyl, C6-18 aryl, or C4-18 heteroaryl, or R1 and R2 are fused to be C6-18 aralkyl; R3 is H, C1-10 alkyl, C3-10 cycloalkyl, C6-10 aryl, or C4-10 heteroaryl. Preferably, R1 and R2 are each independently H, C1-10 alkyl, C3-10 cycloalkyl, C6-14 aryl, or C4-12 heteroaryl, or R1 and R2 are fused to be C6-12 aralkyl; R3 is H, C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, or C4-10 heteroaryl. More preferably, R1 and R2 are each independently H, C1-6 alkyl, C3-6 cycloalkyl, C6-14 aryl, or C4-10 heteroaryl, or R1 and R2 are fused to be C6-10 aralkyl; R3 is H, C1-6 alkyl, or C3-6cycloalkyl.
In addition, in the compound (I) with an unsaturated double bond, R, R2 and R3 are not H at the same time
In the present disclosure, the catalyst may be represented by Formula (II). In the catalyst represented by Formula (II), L1 is a ligand and preferably selected from the group consisting of OTf, OTs, NTf2, halogen, RC(O)CH2C(O)R, OAc, OC(O)R, OC(O)CF3, OMe, OEt, O-iPr, and butyl, wherein R is alkyl (preferably C1-6 alkyl, more preferably C1-3 alkyl). Furthermore, L2 is a ligand and preferably selected from the group consisting of Cl, H2O, CH3OH, EtOH, THF, CH3CN,
and ligand containing C═N unit.
In the present disclosure, the “ligand containing C═N unit” may comprise pyridine, oxazole, oxazoline, or imidazole. However, the present disclosure is not limited thereto. Specific example comprises 2,2′-bipyridyl, 3-chloropyridine, 2,6-dichloropyridine, 3,5-dichloropyridine, 2,6-di-tert-butylpyridine, 1-methylimidazole, 1,2-dimethylimidazole. However, the present disclosure is not limited thereto.
In one embodiment of the present disclosure, the “ligand containing C═N unit” may be represented by Formula (IV):
wherein, R4 and R5 are each independently halogen, nitro, C1-10 alkyl, C6-18 aryl, or C4-18 heteroaryl. Preferably, R4 and R5 may be each independently Cl, Br, NO2 or C1-10 alkyl.
In another embodiment, the “ligand containing C═N unit” may be represented by Formula (V):
wherein R6 and R7 are each independently H, C1-5 alkyl or C3-4 cycloalkyl.
Further, in the catalyst represented by Formula (II), M may be a metal selected from the group consisting of IVB, VB, VIB, and actinides. In one aspect, M is a group IVB transition element, m is 1 and y is 2; wherein M may be Ti, Zr, or Hf. In another aspect, M is a group VB transition element, m is 1 and y is 2 or 3; wherein M may be V or Nb. In another aspect, M is a group VIB transition element, m is 1 and y is 4; wherein M may be Mo, W, or Cr. In another aspect, M is a group VIB transition element, m is 2 and y is 2; wherein M is Mo, W, or Cr. In yet another aspect, M is selected from the actinides, m is 2 and y is 2; wherein M is U.
In addition, in the catalyst of Formula (II), z may be an integer greater than or equal to 0. When z is 0, the specific example of the catalyst of Formula (II) may be MoO2Cl2, V(O)Cl3, V(O)O-iPr)3, V(O)Cl2, V(O)(OAc)2, V(O)(O2CCF3)2, Ti(O)(acac)2, Zr(O)Cl2, Hf(O)Cl2, Nb(O)Cl2, MoO2(acac)2, V(O)(OTs)2, VO(OTf)2, or V(O)(NTf2)2. However, the present disclosure is not limited thereto. When z is an integer greater than 0, the specific example of the catalyst of Formula (II) may be any of formulas (II-1) to (II-4):
However, the present disclosure is not limited thereto.
The trifluoromethyl-containing reagent according to the present disclosure may be a monotrifluoromethyl- or perfluoroalkyl-containing reagent. The specific example comprises 3,3-Dimethyl-1-(trifluoromethyl)-1,2-benziodoxole, 3,3-Dimethyl-1-(perfluroalkyl)-1,2-benziodoxole, 3-oxo-1-(trifluoromethyl)-1,2-benziodoxole, 3-oxo-1-(perfluroalkyl)-1,2-benziodoxole, trifluomethyl dibenzothiophenium salts, perfluoroalkyl dibenzothiophenium salt, CF3SO2Na, and CF3(CF2), SO2Na (n=1-6). However, the present disclosure is not limited thereto.
In the compound represented by Formula (III), R1 and R2 are each independently H, C1-20 alkyl, C3-20 cycloalkyl, C6-18 aryl, or C4-18 heteroaryl, or R1 and R2 fused to be C6-18 aralkyl group. Preferably, R1 and R2 are each independently H, C1-10 alkyl, C3-10 cycloalkyl, C6-14 aryl, or C4-12 heteroaryl, or R1 and R2 fuse to be C6-12 aralkyl group. More preferably, R1 and R2 are each independently H, C1-6 alkyl, C3-6 cycloalkyl, C6-12 aryl, or C4-10 heteroaryl, or R1 and R2 fused to be C6-10 aralkyl group. In one embodiment of the present disclosure, R1 and R2 are not H at the same time.
In the present disclosure, step (B) may further obtain a trifluoroketone- or trifluoroaldehyde-containing compound, trifluoroalkyl alcohol or a combination thereof.
wherein R3 is H, C1-10 alkyl, C3-10 cycloalkyl, C6-10 aryl, or C4-10 heteroaryl; n is an integer of 0 or 1 to 6.
In one embodiment of the present disclosure, R3 is preferably H, C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, or C4-10 heteroaryl; n is an integer of 0 or 1 to 3. More preferably, R3 is preferably H, C1-6 alkyl, or C3-6 cycloalkyl; n is 0 or 1.
In another aspect of the present disclosure, the step (B) may further comprise adding an additive to the mixture of the compound with an unsaturated double bond and the trifluoromethyl-containing reagent, wherein the additive may be trimethylsilyl cyanide (TMSCN), anhydride or a combination thereof. However, the present disclosure is not limited thereto.
Herein, the term “alkyl” of the present disclosure includes unsubstituted alkyl or alkyl group substituted with halogen, nitro, alkenyl, cycloalkyl, alkoxy, aryl, or heteroaryl. The terms “cycloalkyl”, “aryl”, “heteroaryl” and “aralkyl” include unsubstituted groups or groups substituted with alkyl, halogen, nitro, alkenyl, cycloalkyl, alkoxy, aryl, or heteroaryl.
In summary, the present disclosure introduces a trifluoromethyl-containing reagent into an oxidative cleavage reaction. The reaction can use air or oxygen as an oxidant source under mild conditions, and the reaction is conducted using a proper catalyst to obtain a corresponding ketone or aldehyde. In addition, because of the introduction of the trifluoromethyl reagent, the other half of the oxidative cleavage reaction will be converted into trifluoromethyl or perfluoromethylketone, or trifluoromethyl aldehyde, perfluoroalkyl aldehyde, and trifluoromethyl or perfluroalkyl ethanol, which can be further used.
Other objects, advantages, and novel features of the invention will become more apparent from the following detailed description when taken in conjunction with the accompanying drawings.
Different embodiments of the present invention are provided in the following description. These embodiments are meant to explain the technical content of the present invention, but not meant to limit the scope of the present invention. A feature described in an embodiment may be applied to other embodiments by suitable modification, substitution, combination, or separation.
Preparation of an Unsaturated Double Bond with an Unsaturated Double Bond
In a flame-dried, 50-mL, two-necked, round-bottomed flask was placed methyltriphenylphosphonium bromide (3.0 equiv) dissolved in 1 mL THF (0.2 M) at 0° C. Then added tert-BuOK (3.0 equiv) stirred at 0° C. After 30 minutes, add ketone or aldehyde (1.0 equiv) and let it warm to room temperature. After having been complete of the reaction, the reaction was quenched with H2O and extracted with EtOAc for three times. The combined organic layers dried over MgSO4, and the filtrate was concentrated. The crude product was purified using flash column chromatography on silica gel with pure hexane as eluent to afford styrene derivatives.
1H NMR (CDCl3, 400 MHz) δ 8.19 (d, J=9.0 Hz, 2H), 7.60 (d, J=9.1 Hz, 2H), 5.52 (t, J=0.8 Hz, 1H), 5.29 (t, J=1.3 Hz, 1H), 2.19 (dd, J=1.5, 0.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 147.6, 147.0, 141.6, 126.2, 123.6, 116.4, 21.6; TLC Rf 0.47 (hexane); HRMS (FI) Calcd for C9H9NO2: 163.0628, found: 163.0628.
1H NMR (CDCl3, 500 MHz) δ 7.47 (d, J=9.0 Hz, 2H), 7.05 (d, J=8.5 Hz, 2H), 5.34 (s, 1H), 5.08 (s, 1H), 2.30 (s, 3H), 2.14 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ169.5, 150.0, 142.4, 140.0, 126.5, 121.2, 112.6, 21.8, 21.1; TLC Rf 0.38 (hexane); HRMS (FI) Calcd for C11H12O2: 176.0832, found: 176.0828.
1H NMR (CDCl3, 400 MHz) δ7.43 (d, J=8.9 Hz, 2H), 6.87 (d, J=8.9 Hz, 2H), 5.29 (dq, J=1.6, 0.7 Hz, 1H), 4.99 (quin, J=1.5 Hz, 1H), 2.13 (t, J=0.9 Hz, 3H), 3.82 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 159.0, 142.5, 133.7, 126.6, 113.5, 110.6, 55.3, 21.9; TLC Rf 0.42 (hexane); HRMS (FI) Calcd for C10H12O: 148.0883, found: 148.0887.
1H NMR (400 MHz, CDCl3) δ 7.87-7.82 (m, 4H), 7.71-7.68 (m, 1H), 7.51-7.44 (m, 2H), 5.56 (s, 1H), 5.22-5.21 (m, 1H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ143.0, 138.3, 133.3, 132.8, 128.2, 127.7, 127.5, 126.1, 125.8, 124.2, 123.9, 113.0, 21.8; TLC Rf 0.49 (hexane); HRMS (FI) Calcd for C3H10: 168.0934, found: 168.0928.
1H NMR (CDCl3, 400 MHz) δ 8.55 (d, J=6 Hz, 2H), 7.33 (d, J=5.2 Hz, 2H), 5.57 (d, J=0.6 Hz, 1H), 5.26 (d, J 1.0 Hz, 2H), 2.14 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 150.7, 149.4, 148.2, 140.7, 121.0, 119.9, 115.8, 20.6; TLC Rf 0.30 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C8H9N: 119.0730, found: 119.0730.
1H NMR (CDCl3, 400 MHz) 8.68 (td, J=4, 0.8 Hz, 1H), 8.03 (dd, J=8.0, 0.8 Hz, 1H), 7.82 (dt, J=7.8, 1.6 Hz, 1H), 7.44-7.48 (m, 1H), 2.72 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 199.4, 153.1, 148.6, 136.4, 136.1, 126.7, 121.1, 25.3; TLC Rf0.25 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C8H9N: 119.0730, found: 119.0729.
1H NMR (400 MHz, CDCl3) δ7.15 (dd, J=5.1, 1.1 Hz, 1H), 7.02 (dd, J=3.6, 1.1 Hz, 1H), 6.96 (dd, J=5.1, 3.6 Hz, 1H), 5.37 (s, 1H), 4.94 (m, 1H), 2.14 (m, 3H); 13C NMR (125 MHz, CDCl3) δ145.8, 137.1, 127.2, 124.2, 123.5, 111.1, 21.8; TLC Rf 0.43 (hexane); HRMS (FI) Calcd for C7H8S: 124.0341, found: 124.0340.
1H NMR (CDCl3, 400 MHz) δ 4.66 (s, 2H), 1.90-1.82 (m, 2H), 1.78-1.1.71 (m, 7H), 1.30-1.11 (m, 6H); 13C NMR (CDCl3, 100 MHz) δ 151.3, 107.8, 45.5, 32.0, 26.8, 26.4, 20.9; TLC Rf0.6 (hexane); HRMS (FI) Calcd for C9H16: 124.1247, found: 124.1243.
1H NMR (CDCl3, 400 MHz) δ 7.51-7.34 (m, 5H), 5.57 (s, 1H), 5.50 (s, 1H), 4.40 (s, 2H); 13C NMR (CDCl3, 100 MHz) δ 144.2, 137.6, 128.5, 128.3, 126.1, 117.2, 34.2; TLC Rf 0.51 (hexane); HRMS (EI) Calcd for C9H9Br: 195.9882, found: 195.9882.
1H NMR (CDCl3, 400 MHz) δ 7.62-7.59 (m, 2H), 7.37-7.26 (m, 3H), 5.28 (s, 1H), 4.94 (s, 1H), 1.68-1.64 (m, 1H), 0.87-0.82 (m, 2H), 0.61-0.58 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ149.4, 141.6, 128.1, 127.4, 126.1, 109.0, 15.6, 6.7; TLC Rf 0.48 (hexane); HRMS (F) Calcd for C11H12: 144.0934, found: 144.0936.
1H NMR (CDCl3, 400 MHz) δ 7.36-7.25 (m, 5H), 5.14 (s, 1H), 5.01 (s, 1H), 2.43 (t, J=11.6 Hz, 1H), 1.86-1.70 (m, 5H), 1.38-1.13 (m, 5H); 13C NMR (CDCl3, 100 MHz) δ 154.99, 142.97, 128.10, 126.97, 126.62, 110.31, 42.58, 32.71, 26.84, 26.45; TLC Rf 0.5 (hexane); HRMS (FI) Calcd for C14H18: 186.1403, found: 186.1402.
1H NMR (CDCl3, 400 MHz) δ 7.31-7.26 (m, 3H), 7.16-7.14 (m, 2H), 5.18 (d, J=2.0 Hz, 1H), 4.77 (d, J=1.6 Hz, 1H), 1.13 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 159.8, 143.5, 129.0, 127.2, 126.2, 111.5, 36.1, 29.6; TLC Rf 0.4 (hexane); HRMS (FI) Calcd for C12H16: 160.1247, found: 160.1247.
1H NMR (CDCl3, 400 MHz) δ7.52-7.50 (m, 1H), 7.28-7.20 (m, 3H), 5.46 (t, J=2.4 Hz, 1H), 5.04 (t, J=2.4 Hz, 1H), 3.01-2.98 (m, 2H), 2.83-2.78 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ150.6, 146.7, 141.1, 128.2, 126.4, 125.3, 120.6, 102.4, 31.2, 30.1; TLC Rf 0.5 (hexane); HRMS (FI) Calcd for C10H10: 130.0777, found: 130.0776.
Synthesis of Catalyst (II)-1
In the present embodiment, the catalyst can be synthesized according to the following chemical equation.
V(O)SO4(aq)+BaX2(aq)→V(O)X2(aq)+BaSO4(s)
V(O)SO4(aq)+Ba(OC(O)R)2(aq)→V(O)(OC(O)R)2(aq)+BaSO4(s)
V(O)SO4(aq)+Ba(OTf)2(aq)→V(O)(OTf)2(aq)+BaSO4(s)
V(O)SO4(aq)+Ba(OTs)2(aq)→V(O)(OTs)2(aq)+BaSO4(s)
V(O)SO4(aq)+Ba[(O3SC6H4CHCH2)n]2(aq)→V(O)[(O3SC6H4CHCH2)n]2(aq)+BaSO4(s)
In a flame-dried, 50-mL, two-necked, round-bottomed flask was placed vanadyl sulfate-VOSO4-5H2O (VOSO4.5H2O, 2.5 mmol) followed by addition of anhydrous MeOH (2.5 mL). To the above solution, a solution of Ba(OTf)2 (1 equiv, 2.5 mmol) in MeOH (2.5 mL) was slowly added at ambient temperature. After stirring for 30 minutes, the reaction mixture became turbid with copious amount of barium sulfate precipitation. Centrifugation (6000 rpm) for the mixture was performed for 30 minutes. The decanted solution was evaporated to give a dark green or faint blue solid which was further dried at 120° C. for 4 hours in vacuo. The resultant catalyst can be stored at ambient temperature for several weeks in dry cabinet and can be used directly.
To the solution of 3,5-di-tert-butyl-2-hydroxybenzaldehyde (1217 mg, 5.0 mmol, 1.0 equiv) in MeOH (12.5 mL) was added L-tert-leucine (721 mg, 5.5 mmol, 1.1 equiv) or other 18 natural L-α-amino acids (721 mg, 5.5 mmol, 1.1 equiv) and NaOAc (902 mg, 11.0 mmol, 2.2 equiv). After stirring at 80° C. for 18 hours, the reaction mixture was gradually cooled to ambient temperature and a solution of VOSO4.5H2O (1392 mg, 5.5 mmol, 1.1 equiv) in MeOH (5.0 mL) was added. After the reaction was performed at ambient temperature for 6 hours, the reaction mixture was concentrated under reduced pressure. The resulting dark black solid was washed with water (5×30 mL) and dried in vacuo to afford a pure oxidovanadium(IV) catalyst. The corresponding analytically pure oxidovanadium(V) methoxide (or hydroxide) complex (11-1) was obtained by re-crystallization from oxygen saturated MeOH.
Catalyst (II-1)
Yield: 84%; black solid. 1H NMR (CD3OD, 500 MHz) S 8.60 (bs, 1H), 7.68 (d, J=2.2 Hz, 1H), 7.48 (d, J=2.3 Hz, 1H), 4.14 (s, 1H), 1.47 (s, 9H), 1.35 (s, 9H), 1.21 (s, 9H); 51V NMR (CD3OD, 132 MHz) δ −565.0; 13C NMR (CD3OD, 126 MHz) δ 180.1, 168.9, 161.7, 143.5, 138.6, 132.4, 129.5, 129.4, 121.9, 84.7, 49.6, 49.3, 49.2, 49.0, 48.8, 48.6, 48.4, 38.3, 36.3, 35.3, 31.8, 30.3, 28.1; IR (KBr) 3370 (br, w), 2959 (w), 2871 (w), 1698 (m), 1668 (m), 1620 (s, C═N), 1580 (w), 1524 (m, COO), 1480 (w), 1456 (w), 1373 (w), 1322 (w), 1285 (w), 1182 (w), 1071 (w), 986 (m, V═O); [α]D34 +36.53 (c 0.1, CH2Cl2); TLC Rf 0.37 (CH3OH/CH2Cl2, 1/8); HRMS (ESI) [M+H]+ Calcd for C22H34NO5V: 444.1959, found: 444.1949.
Catalyst (II-2)
Yield: 57%; black solid. 1H NMR (CD3OD, 400 MHz) δ 8.54 (bs, 1H), 7.66 (d, J=2.4 Hz, 1H), 7.62 (d, J=2.4 Hz, 1H), 4.15 (s, 1H), 3.33 (s, OCH3), 1.44 (s, 9H), 1.18 (s, 9H); 51V NMR (CD3OD, 105 MHz) δ −567.6; 13C NMR (CD3OD, 126 MHz) δ 167.7, 142.3, 136.9, 136.2, 135.0, 134.6, 123.7, 111.9, 84.7, 49.8, 38.3, 37.2, 36.2, 29.9, 28.0, 27.4; IR (KBr) 2965 (s), 2913 (m), 2869 (m), 1663 (s), 1615 (s, C═N), 1578 (m), 1548 (m, COO), 1480 (w), 1429 (m), 1368 (m), 1320 (m), 1297 (s), 1181 (m), 1055 (w), 1031 (w), 993 (m, V═O); [α]D34 −126.4 (c 0.1, CH3OH); TLC Rf0.20 (CH3OH/CH2Cl2, 1/9); HRMS (ESI) [M+H]+ Calcd for C18H25BrNO5V: 466.0427; found: 466.0428.
Catalyst (II-3)
Yield: 75%; black solid. 1H NMR (CD3OD, 400 MHz) δ 8.56 (bs, 1H), 7.96 (d, J=2.3 Hz, 1H), 7.78 (d, J=2.3 Hz, 1H), 4.18 (s, 1H), 1.20 (s, 9H); 51V NMR (CD3OD, 105 MHz) δ −557.0; 13C NMR (CD3OD, 126 MHz) δ 179.1, 167.2, 159.6, 141.7, 136.7, 123.6, 114.8, 110.9, 84.8, 49.9, 38.2, 28.1, 36.2, 29.9, 28.0, 27.4; IR (KBr) 3370 (br, w), 2959 (w), 2871 (w), 1698 (m), 1668 (m), 1620 (s, C═N), 1580 (w), 1524 (m, COO), 1480 (w), 1456 (w), 1373 (w), 1322 (w), 1285 (w), 1182 (w), 1071 (w), 986 (m, V═O); [α]D34 −40.8 (c 0.1, CH2Cl2); TLC Rf0.12 (CH3OH/CH2Cl2, 1/10); HRMS (ESI) [M+H]+ Calcd for C14H16Br2NO5V: 489.8880, found: 489.8888.
Catalyst (II-4)
Yield: 81%; black solid. 1H NMR (CD3OD, 400 MHz) δ 8.71 (bs, 1H), 8.54 (d, J=2.6 Hz, 1H), 8.39 (d, J=2.5 Hz, 1H), 4.24 (s, 1H), 3.31 (s, OCH3), 1.49 (s, 9H), 1.22 (s, 9H); 51V NMR (CD3OD, 105 MHz) δ 549.8,-568.8; 13C NMR (CD3OD, 126 MHz) δ 168.0, 140.5, 139.1, 130.1, 130.0, 128.4, 127.6, 121.5, 84.9, 38.3, 36.5, 29.7, 28.0; IR (KBr) 2965 (w), 2916 (w), 2879 (w), 1627 (m, C═N), 1598 (m, COO), 1509 (w), 1326 (m), 1326 (w), 1225 (w), 1187 (w), 1113 (w), 1034 (w), 990 (w), 927 (w, V═O); MS (ESI) 850 (M2O+H2O, 90), 419 (MOH+H+, 9), 417 (MOH-1+, 100); [α]D34 83.93 (c 0.1, CH3OH); TLC Rf 0.30 (CH3OH/CH2Cl2, 1/4); Anal. Calcd. For [(H2O)MOH]: C, 46.80; H, 5.78; N, 6.42. Found: C, 45.57; H, 5.83; N, 6.15.
Oxidative Cleavage
In a flame-dried, 50-mL, two-necked, round-bottomed flask was placed 5 mol % VO(OTf)2. 5H2O (11.8 mg, 0.025 mmol, 0.05 equiv) and 6 mol % additive (21.5 mg, 0.030 mmol, 0.06 equiv) and trifluoromethyl- or perfluoromethyl-containing reagent (346.6 mg, 1.05 mmol, 1.5 equiv) dissolved in 2.5 mL acetone. Then, α-methylstyrene (65 μL, 0.70 mmol, 1.0 equiv) was added. After having the reaction finished, the solvent was removed in vacuo, and the crude product was purified by using flash column chromatography on silica gel (ethyl acetate/hexane=1/8) to afford the product. The result is shown in Table 1.
It can be found in Table 1 that the yield is low (28%) when the oxidative cleavage was performed with commercial catalyst Cu(CH3CN)4PF6. The yield can be doubled or tripled when the catalyst V(O)(OTf)2 was used in the reaction. When the reaction was performed with the catalyst of Formula (II-1) to Formula (II-4), the yield (81-97%) is significantly improved.
In aflame-dried, 25-mL, two-necked, round-bottomed flask was placed 5 mol % catalyst (eq II-3) and trifluoromethyl- or perfluoromethyl-containing reagent (1.5 equiv) dissolved in acetone (I mL). Then, a compound (1-1) (1.0 equiv) with an unsaturated double bond was added. After having the reaction finished, the solvent was removed in vacuo, and the crude product was purified by using flash column chromatography on silica gel (ethyl acetate/hexane=1/8) to afford the product. The result is shown in Table 2.
With the catalyst of Formula (II-3) of the present disclosure, the oxidative cleavage is carried out without adding additives. The resultant product with high isolated yield (90-97%) can be obtained in the aromatic system, and the reaction time is 46 to 144 hours. Also, the resultant product with high isolated yield (90-93%) can be obtained in the heteroaryl system, and the reaction time is 45 to 144 hours. The isolated yield is up to 92% in the cycloalkyl system, and the reaction time is 50 hours.
In addition, through 19F NMR spectroscopic analysis, it is found that the other half of the main oxidative cleavage is converted to trifluoromethylketone or trifluoroaldehyde and trifluoroethanol (or the corresponding trifluoromethyl alcohol) rather than formaldehyde or 1,3,5-trioxane after the oxidative cleavage.
The reaction was performed in the same manner as described above, and the result is shown in Table 3.
It was found that if R1 of the compound (I) with an unsaturated double bond was designated as phenyl to perform the oxidative cleavage reaction, the isolated yield was 91-92% with a longer reaction time (192-193 hours) when R2 was an alkyl system. When R2 was a cycloalkyl system, the yield is 89-95%, and the reaction time was shortened to 90-96 hours. In addition, when R2 is aryl or R1 and R2 are fused to be an aralkyl system, the yield is up to 95%, and the reaction time is significantly reduced to 45-48 hours.
The reaction was performed in the same manner as described above, and the result is shown in Table 4.
athe reaction was performed at 50° C.
The reaction was performed in the same manner as described above, and the result is shown in Table 5.
bX is halogen (F, Cl, Br, I)
When the R2 and R3 of the compound (I) with an unsaturated double bond is H, the corresponding benzaldehyde, trifluoroaldehyde and trifluoroethanol can be obtained.
1H NMR (CDCl3, 400 MHz) δ 7.97-7.95 (m, 2H), 7.58-7.54 (m, 1H), 7.84-7.44 (m, 2H), 2.6 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 198.0, 137.0, 133.0, 128.4, 128.2, 26.4; TLC Rf 0.32 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C8H8O: 120.0570, found: 120.0569.
1H NMR (CDCl3, 400 MHz) δ 7.86-7.85 (m, 2H), 7.26 (d, J=7.6 Hz, 2H), 2.58 (s, 3H), 2.41 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 197.8, 143.9, 134.7, 129.2, 128.4, 26.5, 21.60; TLC Rf 0.25 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C9H10O: 134.0726, found: 134.0725.
1H NMR (CDCl3, 400 MHz) δ 8.05-8.02 (m, 2H), 7.71-7.68 (m, 2H), 7.65-7.62 (m, 2H), 7.50-7.45 (m, 2H), 7.43-7.38 (m, 2H), 2.65 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ197.7, 145.8, 139.9, 135.9, 128.9, 128.9, 128.2, 127.3, 127.2, 26.6; TLC Rf0.3 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C14H12O: 196.0883, found: 196.0822.
1H NMR (CDCl3, 400 MHz) δ 7.91-7.87 (m, 2H), 7.45-7.41 (m, 2H), 2.59 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 196.7, 139.5, 135.4, 129.6, 128.8, 26.4; TLC Rf 0.23 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C8H7ClO: 154.0180, found: 154.0181.
1H NMR (CDCl3, 400 MHz) δ 7.84-7.81 (m, 2H), 7.62-7.60 (m, 2H), 2.59 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 196.9, 135.8, 131.9, 129.8, 128.3, 26.5; TLC Rf 0.28 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C8H7BrO: 197.9675, found: 197.9676.
1H NMR (CDCl3, 400 MHz) δ 8.33-8.29 (m, 2H), 8.12-8.09 (m, 2H), 2.68 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 196.2, 150.4, 141.4, 129.3, 123.8, 26.9; TLC Rf 0.35 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C8H7NO3: 165.0420, found: 165.0421.
1H NMR (CDCl3, 400 MHz) δ 8.00-7.97 (m, 2H), 7.20-7.16 (m, 2H), 2.58 (s, 3H), 2.31 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 196.8, 168.8, 154.3, 134.7, 129.9, 121.7, 26.5, 21.1; TLC Rf0.30 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C10H10O3: 178.0624, found: 178.0625.
1H NMR (CDCl3, 400 MHz) δ 7.95-7.92 (m, 2H), 6.95-6.91 (m, 2H), 3.87 (s, 3H), 2.55 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 196.7, 163.5, 130.6, 130.4, 113.7, 55.4, 26.3; TLC Rf 0.35 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C9H10O2: 150.0675, found: 105.0676.
1H NMR (CDCl3, 400 MHz) δ 7.77-7.37 (m, 2H), 7.39-7.26 (m, 2H), 2.59 (s, 3H), 2.41 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 198.3, 138.3, 137.1, 133.8, 128.7, 128.4, 125.5, 26.5, 21.2; TLC Rf0.21 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C9H10O: 134.0726, found: 134.0724.
1H NMR (CDCl3, 400 MHz) δ 7.71-7.68 (m, 1H), 7.40-7.36 (m, 1H), 7.29-7.24 (m, 2H), 2.58 (s, 3H), 2.53 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 201.7, 138.3, 137.6, 132.0, 131.4, 129.3, 125.6, 29.5, 21.5; TLC Rf 0.25 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C9H10O: 134.0726, found: 134.0724.
1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 8.04 (dd, J=8.6, 1.4 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.91-7.87 (m, 2H), 7.63-7.54 (m, 2H), 2.74 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 198.1, 135.6, 134.5, 132.5, 130.2, 129.5, 128.4, 128.4, 127.8, 126.7, 123.9, 26.7; TLC Rf 0.20 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C2H10O: 170.0726; found: 170.0721.
1H NMR (CDCl3, 400 MHz) δ 8.80 (dd, J=4.4, 1.6 Hz, 2H), 7.72 (dd, J=4.4, 1.6 Hz, 2H), 2.62 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 196.6, 150.2, 142.0, 120.5, 25.9; TLC Rf 0.20 (EtOAc/Hexane=1/3); HRMS (FI) Calcd for C7H7NO: 121.0522, found: 121.0522.
1H NMR (CDCl3, 400 MHz) δ8.68 (td, J=4.0, 0.8 Hz, 1H), 8.03 (dd, J=8.0, 0.8 Hz, 1H), 7.82 (dt, J=7.8, 1.6 Hz, 1H), 7.44-7.48 (m, 1H), 2.72 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 199.4, 153.1, 148.6, 136.4, 136.1, 126.7, 121.1, 25.3; TLC Rf 0.25 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C7H7NO: 121.0522, found: 121.0521.
1H NMR (400 MHz, CDCl3) δ 7.70 (dd, J=3.5, 1.2 Hz, 2H), 7.64 (dd, J=4.9, 1.2 Hz, 1H), 7.13 (dd, J=4.9, 3.5 Hz, 2H), 2.57 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 190.6, 144.5, 133.7, 132.4, 128.0, 26.8; TLC Rf 0.30 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C6HOS: 126.0134, found: 126.0133.
1H NMR (CDCl3, 400 MHz) δ 2.34-2.30 (m, 1H), 2.11 (s, 3H), 2.19-1.84 (m, 2H), 1.79-1.74 (m, 2H), 1.67-1.63 (m, 1H), 1.33-1.19 (m, 5H); 13C NMR (CDCl3, 100 MHz) δ 212.3, 51.4, 28.4, 27.8, 25.8, 25.6; TLC Rf 0.21 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C8H14O: 126.1039, found: 126.1036.
1H NMR (CDCl3, 400 MHz) δ 8.00-7.98 (m, 2H), 7.64-7.60 (m, 1H), 7.52-7.50 (m, 2H), 4.46 (s, 2H); 13C NMR (CDCl3, 125 MHz) δ 191.3, 134.0, 134.0, 128.9, 128.8, 30.9; TLC Rf 0.25 (EtOAc/Hexane=1/20); HRMS (EI) Calcd for C8H7BrO: 197.9675, found: 197.9679.
1H NMR (CDCl3, 400 MHz) δ 8.03-8.00 (m, 2H), 7.59-7.54 (m, 1H), 7.50-7.45 (m, 2H), 2.71-2.65 (m, 2H), 1.27-1.23 (m, 2H), 1.07-1.02 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ 200.5, 137.9, 132.6, 128.44, 127.9, 17.0, 11.5; TLC Rf 0.20 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C10H10O: 146.0726, found: 146.0727.
1H NMR (CDCl3, 400 MHz) δ 7.94 (d, J=7.2 Hz, 2H), 7.55 (tt, J=7.2, 2.0 Hz, 1H), 7.46 (t, J=7.4 Hz, 2H), 3.26 (tt, J=11.2, 3.2 Hz, 1H), 1.91-1.82 (m, 4H), 1.76-1.72 (m, 1H), 1.55-1.25 (m, 5H); 13C NMR (CDCl3, 100 MHz) δ 203.9, 136.4, 132.7, 128.6, 128.3, 45.6, 29.4, 26.0, 25.9; TLC Rf 0.3 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C13H16OF3: 188.1196, found: 188.1195.
1H NMR (CDCl3, 400 MHz) δ 7.70-7.67 (m, 2H), 7.47-7.37 (m, 3H), 1.35 (s, 9H); 13C NMR (CDCl3, 125 MHz) δ 209.3, 138.6, 130.7, 128.0, 127.8, 44.2, 28.0; TLC Rf 0.4 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C11H14O: 162.1039, found: 162.1038.
1H NMR (CDCl3, 400 MHz) δ 7.82-7.80 (m, 4H), 7.62-7.57 (m, 2H), 7.51-7.47 (m, 4H); 13C NMR (CDCl3, 125 MHz) δ 196.7, 137.5, 132.4, 123.0, 128.2; TLC Rf0.35 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C13H10O: 182.0726, found: 182.0725.
1H NMR (CDCl3, 400 MHz) δ 7.76 (d, J=7.2 Hz, 1H), 7.61-7.57 (m, 1H), 7.50-7.47 (m, 1H), 7.39-7.35 (m, 1H), 3.15 (t, J=6.0 Hz, 2H), 2.71-2.68 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ 206.9, 155.1, 137.0, 134.5, 127.2, 126.6, 123.6, 36.1, 25.7; TLC Rf0.3 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C9H8O: 132.0570, found: 132.0570.
CF3CH2OH (Trifluoroethanol): 1H NMR (400 MHz, CDCl3) δ 3.92 (q, J=8.8 Hz, 2H), 3.21 (br, 1H, OH); 19F NMR (470 MHz, CDCl3) δ −79.08 (s).
CF3CHO (Trifluoroacetaldehyde; b.p.−18° C.): 19F NMR (470 MHz, CDCl3) δ −84.62 (s)
1H NMR (CDCl3, 500 MHz) δ 3.98 (sept, J=6.5 Hz, 1H), 3.17 (s, 1H, OH), 1.38 (d, J=6.5 Hz, 3H); 19F NMR (470 MHz, CDCl3) δ −81.4 (s).
1H NMR (CDCl3, 500 MHz) δ 2.48 (s, 3H); 19F NMR (470 MHz, CDCl3) δ −80.0 (s).
Although the present invention has been explained in relation to its preferred embodiment, it is to be understood that many other possible modifications and variations can be made without departing from the spirit and scope of the invention as hereinafter claimed.
| Number | Date | Country | Kind |
|---|---|---|---|
| 109100028 | Jan 2020 | TW | national |
