METHOD FOR OXIDATIVE CLEAVAGE OF COMPOUNDS WITH UNSATURATED DOUBLE BOND

Abstract

A method for oxidative cleavage of a compound with an unsaturated double bond is provided. The method includes the steps of: (A) providing a compound (I) with an unsaturated double bond, a trifluoromethyl-containing reagent, and a catalyst;

##STR00001## wherein, the catalyst is represented by Formula (II):

M(O).sub.mL.sup.1.sub.yL.sup.2.sub.z(II); wherein, M, L.sup.1, L.sup.2, m, y, z, R.sub.1, R.sub.2 and R.sub.3 are defined in the specification; and (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):

##STR00002##

Claims

1. 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; ##STR00067## wherein, R.sub.1 and R.sub.2 are each independently H, C.sub.1-20 alkyl, C.sub.3-20 cycloalkyl, C.sub.6-18 aryl, or C.sub.4-18 heteroaryl, or R.sub.1 and R.sub.2 are fused to be C.sub.6-18 aralkyl; R.sub.3 is H, C.sub.1-10 alkyl, C.sub.3-10 cycloalkyl, C.sub.6-10 aryl, or C.sub.4-10 heteroaryl, with the proviso that R.sub.1, R.sub.2 and R.sub.3 are not H at the same time; wherein the catalyst is represented by Formula (II):
M(O).sub.mL.sup.1.sub.yL.sup.2.sub.z(II) wherein, M is a metal selected from the group consisting of IVB, VB, VIB, and actinides; L.sup.1 and L.sup.2 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): ##STR00068##

2. The method of claim 1, wherein R.sub.1 and R.sub.2 are each independently H, C.sub.1-10 alkyl, C.sub.3-10 cycloalkyl, C.sub.3-14 aryl, or C.sub.4-10 heteroaryl, or R.sub.1 and R.sub.2 are fused to be C.sub.6-12 aralkyl; R.sub.3 is H, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.6-10 aryl, or C.sub.4-10 heteroaryl.

3. The method of claim 1, wherein L.sup.1 is selected from the group consisting of OTf, OTs, NTf.sub.2, halogen, RC(O)CH.sub.2C(O)R, OAc, OC(O)R, OC(O)CF.sub.3, OMe, OEt, O-iPr, and butyl, wherein R is alkyl.

4. The method of claim 1, wherein L.sup.2 is selected from the group consisting of Cl, H.sub.2O, CH.sub.3OH, EtOH, THF, CH.sub.3CN, ##STR00069## and ligand containing CN unit.

5. The method of claim 4, wherein the ligand containing CN unit comprises pyridine, oxazole, oxazoline, or imidazole.

6. The method of claim 4, wherein the ligand containing CN unit is represented by Formula (IV): ##STR00070## wherein, R.sub.4 and R.sub.5 are each independently halogen, nitro, C.sub.1-10 alkyl, C.sub.6-18 aryl, or C.sub.4-18 heteroaryl.

7. The method of claim 5, wherein the ligand containing CN unit is represented by Formula (V): ##STR00071## wherein R.sub.6 and R.sub.7 are each independently H, C.sub.1-5 alkyl or C.sub.3-6 cycloalkyl.

8. The method of claim 1, wherein the catalyst represented by Formula (II) is MoO.sub.2Cl.sub.2, V(O)Cl.sub.3, V(O)(O-iPr).sub.3, V(O)Cl.sub.2, V(O)(OAc).sub.2, V(O)(O.sub.2CCF.sub.3).sub.2, Ti(O)(acac).sub.2, Zr(O)Cl.sub.2, Hf(O)Cl.sub.2, Nb(O)Cl.sub.2, MoO.sub.2(acac).sub.2, V(O)(OTs).sub.2, VO(OTf).sub.2, or V(O)(NTf.sub.2).sub.2.

9. The method of claim 1, wherein the catalyst represented by Formula (II) is any one of formulas (II-1) to (II-4): ##STR00072##

10. The method of claim 1, wherein the trifluoromethyl-containing reagent is 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 salts, CF.sub.3SO.sub.2Na, or CF.sub.3(CF.sub.2).sub.nSO.sub.2Na, wherein n is an integer of 1 to 6.

11. The method of claim 1, wherein step (B) further obtains a trifluoroketone- or trifluoroaldehyde-containing compound, trifluoroalkyl alcohol or a combination thereof: ##STR00073## wherein R.sub.3 is H, C.sub.1-10 alkyl, C.sub.3-10 cycloalkyl, C.sub.6-10 aryl, or C.sub.4-10 heteroaryl; n is an integer of 0 or 1 to 6.

Description

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0026] 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.

[0027] Preparation of an Unsaturated Double Bond with an Unsaturated Double Bond

##STR00010##

[0028] 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 H.sub.2O and extracted with EtOAc for three times. The combined organic layers dried over MgSO.sub.4, 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.

1-nitro-4-(prop-1-en-2-yl)benzene

[0029] ##STR00011##

[0030] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 147.6, 147.0, 141.6, 126.2, 123.6, 116.4, 21.6; TLC R.sub.f 0.47 (hexane); HRMS (FI) Calcd for C.sub.9H.sub.9NO.sub.2: 163.0628, found: 163.0628.

4-(prop-1-en-2-yl)phenyl acetate

[0031] ##STR00012##

[0032] .sup.1H NMR (CDCl.sub.3, 500 MHz) 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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 169.5, 150.0, 142.4, 140.0, 126.5, 121.2, 112.6, 21.8, 21.1; TLC R.sub.f 0.38 (hexane); HRMS (FI) Calcd for C.sub.11H.sub.12O.sub.2: 176.0832, found: 176.0828.

1-methoxy-4-(prop-1-en-2-yl)benzene

[0033] ##STR00013##

[0034] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.43 (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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 159.0, 142.5, 133.7, 126.6, 113.5, 110.6, 55.3, 21.9; TLC R.sub.f 0.42 (hexane); HRMS (FI) Calcd for C.sub.10H.sub.12O: 148.0883, found: 148.0887.

2-(prop-1-en-2-yl)naphthalene

[0035] ##STR00014##

[0036] .sup.1H NMR (400 MHz, CDCl.sub.3) 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); .sup.13C NMR (100 MHz, CDCl.sub.3) 143.0, 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 R.sub.f 0.49 (hexane); HRMS (FI) Calcd for C.sub.3H.sub.10: 168.0934, found: 168.0928.

4-(prop-1-en-2-yl)pyridine

[0037] ##STR00015##

[0038] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 150.7, 149.4, 148.2, 140.7, 121.0, 119.9, 115.8, 20.6; TLC R.sub.f 0.30 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C.sub.8H.sub.9N: 119.0730, found: 119.0730.

2-(prop-1-en-2-yl)pyridine

[0039] ##STR00016##

[0040] .sup.1H NMR (CDCl.sub.3, 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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 199.4, 153.1, 148.6, 136.4, 136.1, 126.7, 121.1, 25.3; TLC R.sub.f0.25 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C.sub.8H.sub.9N: 119.0730, found: 119.0729.

2-(prop-1-en-2-yl)thiophene

[0041] ##STR00017##

[0042] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.15 (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); .sup.13C NMR (125 MHz, CDCl.sub.3) 145.8, 137.1, 127.2, 124.2, 123.5, 111.1, 21.8; TLC R.sub.f 0.43 (hexane); HRMS (FI) Calcd for C.sub.7H.sub.8S: 124.0341, found: 124.0340.

Prop-1-en-2-ylcyclohexane

[0043] ##STR00018##

[0044] .sup.1H NMR (CDCl.sub.3, 400 MHz) 4.66 (s, 2H), 1.90-1.82 (m, 2H), 1.78-1.1.71 (m, 7H), 1.30-1.11 (m, 6H); .sup.13C NMR (CDCl.sub.3, 100 MHz) 151.3, 107.8, 45.5, 32.0, 26.8, 26.4, 20.9; TLC R.sub.f0.6 (hexane); HRMS (FI) Calcd for C.sub.9H.sub.16: 124.1247, found: 124.1243.

3-bromoprop-1-en-2-yl)benzene

[0045] ##STR00019##

[0046] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.51-7.34 (m, 5H), 5.57 (s, 1H), 5.50 (s, 1H), 4.40 (s, 2H); .sup.13C NMR (CDCl.sub.3, 100 MHz) 144.2, 137.6, 128.5, 128.3, 126.1, 117.2, 34.2; TLC R.sub.f 0.51 (hexane); HRMS (EI) Calcd for C.sub.9H.sub.9Br: 195.9882, found: 195.9882.

(1-cyclopropylvinyl)benzene

[0047] ##STR00020##

[0048] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 149.4, 141.6, 128.1, 127.4, 126.1, 109.0, 15.6, 6.7; TLC R.sub.f 0.48 (hexane); HRMS (F) Calcd for C.sub.11H.sub.12: 144.0934, found: 144.0936.

(1-cyclohexylvinyl)benzene

[0049] ##STR00021##

[0050] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 154.99, 142.97, 128.10, 126.97, 126.62, 110.31, 42.58, 32.71, 26.84, 26.45; TLC R.sub.f 0.5 (hexane); HRMS (FI) Calcd for C.sub.14H.sub.18: 186.1403, found: 186.1402.

(3,3-dimethylbut-1-en-2-yl)benzene

[0051] ##STR00022##

[0052] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 159.8, 143.5, 129.0, 127.2, 126.2, 111.5, 36.1, 29.6; TLC R.sub.f 0.4 (hexane); HRMS (FI) Calcd for C.sub.12H.sub.16: 160.1247, found: 160.1247.

1-methylene-2,3-dihydro-1H-indene

[0053] ##STR00023##

[0054] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.52-7.50 (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); .sup.13C NMR (CDCl.sub.3, 125 MHz) 150.6, 146.7, 141.1, 128.2, 126.4, 125.3, 120.6, 102.4, 31.2, 30.1; TLC R.sub.f 0.5 (hexane); HRMS (FI) Calcd for C.sub.10H.sub.10: 130.0777, found: 130.0776.

[0055] Synthesis of Catalyst (II)-1

[0056] In the present embodiment, the catalyst can be synthesized according to the following chemical equation.

V(O)SO.sub.4(aq)+BaX.sub.2(aq).fwdarw.V(O)X.sub.2(aq)+BaSO.sub.4(s)

V(O)SO.sub.4(aq)+Ba(OC(O)R).sub.2(aq).fwdarw.V(O)(OC(O)R).sub.2(aq)+BaSO.sub.4(s)

V(O)SO.sub.4(aq)+Ba(OTf).sub.2(aq).fwdarw.V(O)(OTf).sub.2(aq)+BaSO.sub.4(s)

V(O)SO.sub.4(aq)+Ba(OTs).sub.2(aq).fwdarw.V(O)(OTs).sub.2(aq)+BaSO.sub.4(s)

V(O)SO.sub.4(aq)+Ba[(O.sub.3SC.sub.6H.sub.4CHCH.sub.2).sub.n].sub.2(aq).fwdarw.V(O)[(O.sub.3SC.sub.6H.sub.4CHCH.sub.2).sub.n].sub.2(aq)+BaSO.sub.4(s)

[0057] In a flame-dried, 50-mL, two-necked, round-bottomed flask was placed vanadyl sulfate-VOSO.sub.4-5H.sub.2O (VOSO.sub.4.5H.sub.2O, 2.5 mmol) followed by addition of anhydrous MeOH (2.5 mL). To the above solution, a solution of Ba(OTf).sub.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.

Synthesis of catalyst (II)-2

[0058] ##STR00024##

[0059] 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--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 VOSO.sub.4.5H.sub.2O (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 (530 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.

[0060] Catalyst (II-1)

##STR00025##

[0061] Yield: 84%; black solid. .sup.1H NMR (CD.sub.3OD, 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); .sup.51V NMR (CD.sub.3OD, 132 MHz) 565.0; .sup.13C NMR (CD.sub.3OD, 126 MHz) 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, CN), 1580 (w), 1524 (m, COO), 1480 (w), 1456 (w), 1373 (w), 1322 (w), 1285 (w), 1182 (w), 1071 (w), 986 (m, VO); [].sub.D.sup.34 +36.53 (c 0.1, CH.sub.2Cl.sub.2); TLC R.sub.f 0.37 (CH.sub.3OH/CH.sub.2Cl.sub.2, 1/8); HRMS (ESI) [M+H].sup.+ Calcd for C.sub.22H.sub.34NO.sub.5V: 444.1959, found: 444.1949.

[0062] Catalyst (II-2)

##STR00026##

[0063] Yield: 57%; black solid. .sup.1H NMR (CD.sub.3OD, 400 MHz) 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, OCH.sub.3), 1.44 (s, 9H), 1.18 (s, 9H); .sup.51V NMR (CD.sub.3OD, 105 MHz) 567.6; .sup.13C NMR (CD.sub.3OD, 126 MHz) 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, CN), 1578 (m), 1548 (m, COO), 1480 (w), 1429 (m), 1368 (m), 1320 (m), 1297 (s), 1181 (m), 1055 (w), 1031 (w), 993 (m, VO); [].sub.D.sup.34 126.4 (c 0.1, CH.sub.3OH); TLC R.sub.f0.20 (CH.sub.3OH/CH.sub.2Cl.sub.2, 1/9); HRMS (ESI) [M+H].sup.+ Calcd for C.sub.18H.sub.25BrNO.sub.5V: 466.0427; found: 466.0428.

[0064] Catalyst (II-3)

##STR00027##

[0065] Yield: 75%; black solid. .sup.1H NMR (CD.sub.3OD, 400 MHz) 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); .sup.51V NMR (CD.sub.3OD, 105 MHz) 557.0; .sup.13C NMR (CD.sub.3OD, 126 MHz) 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, CN), 1580 (w), 1524 (m, COO), 1480 (w), 1456 (w), 1373 (w), 1322 (w), 1285 (w), 1182 (w), 1071 (w), 986 (m, VO); [].sub.D.sup.34 40.8 (c 0.1, CH.sub.2Cl.sub.2); TLC R.sub.f0.12 (CH.sub.3OH/CH.sub.2Cl.sub.2, 1/10); HRMS (ESI) [M+H].sup.+ Calcd for C.sub.14H.sub.16Br.sub.2NO.sub.5V: 489.8880, found: 489.8888.

[0066] Catalyst (II-4)

##STR00028##

[0067] Yield: 81%; black solid. .sup.1H NMR (CD.sub.3OD, 400 MHz) 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, OCH.sub.3), 1.49 (s, 9H), 1.22 (s, 9H); .sup.51V NMR (CD.sub.3OD, 105 MHz) 549.8,-568.8; .sup.13C NMR (CD.sub.3OD, 126 MHz) 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, CN), 1598 (m, COO), 1509 (w), 1326 (m), 1326 (w), 1225 (w), 1187 (w), 1113 (w), 1034 (w), 990 (w), 927 (w, VO); MS (ESI) 850 (M.sub.2O+H.sub.2O, 90), 419 (MOH+H+, 9), 417 (MOH-1.sup.+, 100); [].sub.D.sup.34 83.93 (c 0.1, CH.sub.3OH); TLC R.sub.f 0.30 (CH.sub.3OH/CH.sub.2Cl.sub.2, 1/4); Anal. Calcd. For [(H.sub.2O)MOH]: C, 46.80; H, 5.78; N, 6.42. Found: C, 45.57; H, 5.83; N, 6.15.

[0068] Oxidative Cleavage

##STR00029##

[0069] In a flame-dried, 50-mL, two-necked, round-bottomed flask was placed 5 mol % VO(OTf).sub.2. 5H.sub.2O (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, -methylstyrene (65 L, 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.

TABLE-US-00001 TABLE 1 Trifluoromethyl- Time Yield Embodiment Catalyst containing reagent Additive (h) (%) A-1 Cu(CH.sub.3CN).sub.4PF.sub.6 [00030] [00031] 36 28 A-2 VO(OTf).sub.25H.sub.2O [00032] [00033] 48 56 A-3 VO(OTf).sub.25H.sub.2O CF.sub.3SO.sub.2Na (1.2 eq) [00034] 96 80 A-4 II-1 [00035] 48 81 A-5 II-2 [00036] 48 86 A-6 II-3 [00037] 46 97 A-7 II-4 [00038] 46 82

[0070] It can be found in Table 1 that the yield is low (28%) when the oxidative cleavage was performed with commercial catalyst Cu(CH.sub.3CN).sub.4PF.sub.6. The yield can be doubled or tripled when the catalyst V(O)(OTf).sub.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.

##STR00039##

[0071] 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.

TABLE-US-00002 TABLE 2 Time Yield Embodiment R.sub.1 R.sub.2 (h) (%) B-1 C.sub.6H.sub.5 CH.sub.3 46 97 B-2 4-MeC.sub.6H.sub.4 CH.sub.3 46 96 B-3 4-PhC.sub.6H.sub.4 CH.sub.3 48 90 B-4 4-ClC.sub.6H.sub.4 CH.sub.3 47 95 B-5 4-BrC.sub.6H.sub.4 CH.sub.3 47 93 B-6 4-NO.sub.2C.sub.6H.sub.4 CH.sub.3 144 96 B-7 4-CH.sub.3CO.sub.2C.sub.6H.sub.4 CH.sub.3 72 92 B-8 4-MeOC.sub.6H.sub.4 CH.sub.3 84 95 B-9 3-MeC.sub.6H.sub.4 CH.sub.3 47 91 B-10 2-MeC.sub.6H.sub.4 CH.sub.3 46 93 B-11 2-Naphthyl CH.sub.3 46 90 B-12 4-Py CH.sub.3 120 92 B-13 2-Py CH.sub.3 144 90 B-14 2-Th CH.sub.3 45 93 B-15 cyclohexyl CH.sub.3 50 92

[0072] 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.

[0073] In addition, through .sup.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.

##STR00040##

[0074] The reaction was performed in the same manner as described above, and the result is shown in Table 3.

TABLE-US-00003 TABLE 3 Yield Embodiment R.sub.1 R.sub.2 Time (h) (%) C-1 C.sub.6H.sub.5 CH.sub.2Br 193 91 C-2 C.sub.6H.sub.5 Cy-Pr 90 89 C-3 C.sub.6H.sub.5 Cy-hex 96 95 C-4 C.sub.6H.sub.5 t-Bu 192 92 C-5 C.sub.6H.sub.5 Ph 48 95 C-6 [00041] 45 95

[0075] It was found that if R.sub.1 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 R.sub.2 was an alkyl system. When R.sub.2 was a cycloalkyl system, the yield is 89-95%, and the reaction time was shortened to 90-96 hours. In addition, when R.sub.2 is aryl or R.sub.1 and R.sub.2 are fused to be an aralkyl system, the yield is up to 95%, and the reaction time is significantly reduced to 45-48 hours.

##STR00042##

[0076] The reaction was performed in the same manner as described above, and the result is shown in Table 4.

TABLE-US-00004 TABLE 4 Time Yield Embodiment R.sub.1 R.sub.3 (h) (%) D-1 H CH.sub.3 96 60.sup. D-2 CH.sub.3 CH.sub.3 96 82.sup.a .sup.athe reaction was performed at 50 C.

##STR00043##

[0077] The reaction was performed in the same manner as described above, and the result is shown in Table 5.

TABLE-US-00005 TABLE 5 Time Yield Embodiment Ar (h) (%) E-1 4-XC.sub.6H.sub.4.sup.b 17-24 38-40 E-2 4-CH.sub.3CO.sub.2C.sub.6H.sub.4 26 41 E-3 4-Me or 4-PhC.sub.6H.sub.4 18-19 41-43 E-4 3-ClC.sub.6H.sub.4 96 62 E-5 2-XC.sub.6H.sub.4.sup.b 20-26 58-65 .sup.bX is halogen (F, Cl, Br, I)

[0078] When the R.sub.2 and R.sub.3 of the compound (I) with an unsaturated double bond is H, the corresponding benzaldehyde, trifluoroaldehyde and trifluoroethanol can be obtained.

##STR00044##

[0079] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.97-7.95 (m, 2H), 7.58-7.54 (m, 1H), 7.84-7.44 (m, 2H), 2.6 (s, 3H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 198.0, 137.0, 133.0, 128.4, 128.2, 26.4; TLC R.sub.f 0.32 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C.sub.8H.sub.8O: 120.0570, found: 120.0569.

##STR00045##

[0080] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.86-7.85 (m, 2H), 7.26 (d, J=7.6 Hz, 2H), 2.58 (s, 3H), 2.41 (s, 3H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 197.8, 143.9, 134.7, 129.2, 128.4, 26.5, 21.60; TLC R.sub.f 0.25 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C.sub.9H.sub.10O: 134.0726, found: 134.0725.

##STR00046##

[0081] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 125 MHz) 197.7, 145.8, 139.9, 135.9, 128.9, 128.9, 128.2, 127.3, 127.2, 26.6; TLC R.sub.f0.3 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C.sub.14H.sub.12O: 196.0883, found: 196.0822.

##STR00047##

[0082] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.91-7.87 (m, 2H), 7.45-7.41 (m, 2H), 2.59 (s, 3H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 196.7, 139.5, 135.4, 129.6, 128.8, 26.4; TLC R.sub.f 0.23 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C.sub.8H.sub.7ClO: 154.0180, found: 154.0181.

##STR00048##

[0083] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.84-7.81 (m, 2H), 7.62-7.60 (m, 2H), 2.59 (s, 3H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 196.9, 135.8, 131.9, 129.8, 128.3, 26.5; TLC R.sub.f 0.28 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C.sub.8H.sub.7BrO: 197.9675, found: 197.9676.

##STR00049##

[0084] .sup.1H NMR (CDCl.sub.3, 400 MHz) 8.33-8.29 (m, 2H), 8.12-8.09 (m, 2H), 2.68 (s, 3H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 196.2, 150.4, 141.4, 129.3, 123.8, 26.9; TLC R.sub.f 0.35 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C.sub.8H.sub.7NO.sub.3: 165.0420, found: 165.0421.

##STR00050##

[0085] .sup.1H NMR (CDCl.sub.3, 400 MHz) 8.00-7.97 (m, 2H), 7.20-7.16 (m, 2H), 2.58 (s, 3H), 2.31 (s, 3H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 196.8, 168.8, 154.3, 134.7, 129.9, 121.7, 26.5, 21.1; TLC R.sub.f0.30 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C.sub.10H.sub.10O.sub.3: 178.0624, found: 178.0625.

##STR00051##

[0086] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.95-7.92 (m, 2H), 6.95-6.91 (m, 2H), 3.87 (s, 3H), 2.55 (s, 3H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 196.7, 163.5, 130.6, 130.4, 113.7, 55.4, 26.3; TLC R.sub.f 0.35 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C.sub.9H.sub.10O.sub.2: 150.0675, found: 105.0676.

##STR00052##

[0087] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.77-7.37 (m, 2H), 7.39-7.26 (m, 2H), 2.59 (s, 3H), 2.41 (s, 3H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 198.3, 138.3, 137.1, 133.8, 128.7, 128.4, 125.5, 26.5, 21.2; TLC R.sub.f0.21 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C.sub.9H.sub.10O: 134.0726, found: 134.0724.

##STR00053##

[0088] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 125 MHz) 201.7, 138.3, 137.6, 132.0, 131.4, 129.3, 125.6, 29.5, 21.5; TLC R.sub.f 0.25 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C.sub.9H.sub.10O: 134.0726, found: 134.0724.

##STR00054##

[0089] .sup.1H NMR (400 MHz, CDCl.sub.3) 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); .sup.13C NMR (125 MHz, CDCl.sub.3) 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 R.sub.f 0.20 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C.sub.2H.sub.10O: 170.0726; found: 170.0721.

##STR00055##

[0090] .sup.1H NMR (CDCl.sub.3, 400 MHz) 8.80 (dd, J=4.4, 1.6 Hz, 2H), 7.72 (dd, J=4.4, 1.6 Hz, 2H), 2.62 (s, 1H); .sup.13C NMR (CDCl.sub.3, 100 MHz) 196.6, 150.2, 142.0, 120.5, 25.9; TLC R.sub.f 0.20 (EtOAc/Hexane=1/3); HRMS (FI) Calcd for C.sub.7H.sub.7NO: 121.0522, found: 121.0522.

##STR00056##

[0091] .sup.1H NMR (CDCl.sub.3, 400 MHz) 8.68 (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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 199.4, 153.1, 148.6, 136.4, 136.1, 126.7, 121.1, 25.3; TLC R.sub.f 0.25 (EtOAc/Hexane=1/5); HRMS (FI) Calcd for C.sub.7H.sub.7NO: 121.0522, found: 121.0521.

##STR00057##

[0092] .sup.1H NMR (400 MHz, CDCl.sub.3) 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); .sup.13C NMR (125 MHz, CDCl.sub.3) 190.6, 144.5, 133.7, 132.4, 128.0, 26.8; TLC R.sub.f 0.30 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C.sub.6HOS: 126.0134, found: 126.0133.

##STR00058##

[0093] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 212.3, 51.4, 28.4, 27.8, 25.8, 25.6; TLC R.sub.f 0.21 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C.sub.8H.sub.14O: 126.1039, found: 126.1036.

##STR00059##

[0094] .sup.1H NMR (CDCl.sub.3, 400 MHz) 8.00-7.98 (m, 2H), 7.64-7.60 (m, 1H), 7.52-7.50 (m, 2H), 4.46 (s, 2H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 191.3, 134.0, 134.0, 128.9, 128.8, 30.9; TLC R.sub.f 0.25 (EtOAc/Hexane=1/20); HRMS (EI) Calcd for C.sub.8H.sub.7BrO: 197.9675, found: 197.9679.

##STR00060##

[0095] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 125 MHz) 200.5, 137.9, 132.6, 128.44, 127.9, 17.0, 11.5; TLC R.sub.f 0.20 (EtOAc/Hexane=1/15); HRMS (FI) Calcd for C.sub.10H.sub.10O: 146.0726, found: 146.0727.

##STR00061##

[0096] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 100 MHz) 203.9, 136.4, 132.7, 128.6, 128.3, 45.6, 29.4, 26.0, 25.9; TLC R.sub.f 0.3 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C.sub.13H.sub.16OF.sub.3: 188.1196, found: 188.1195.

##STR00062##

[0097] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.70-7.67 (m, 2H), 7.47-7.37 (m, 3H), 1.35 (s, 9H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 209.3, 138.6, 130.7, 128.0, 127.8, 44.2, 28.0; TLC R.sub.f 0.4 (EtOAc/Hexane=1/20); HRMS (FI) Calcd for C.sub.11H.sub.14O: 162.1039, found: 162.1038.

##STR00063##

[0098] .sup.1H NMR (CDCl.sub.3, 400 MHz) 7.82-7.80 (m, 4H), 7.62-7.57 (m, 2H), 7.51-7.47 (m, 4H); .sup.13C NMR (CDCl.sub.3, 125 MHz) 196.7, 137.5, 132.4, 123.0, 128.2; TLC R.sub.f0.35 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C.sub.13H.sub.10O: 182.0726, found: 182.0725.

##STR00064##

[0099] .sup.1H NMR (CDCl.sub.3, 400 MHz) 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); .sup.13C NMR (CDCl.sub.3, 125 MHz) 206.9, 155.1, 137.0, 134.5, 127.2, 126.6, 123.6, 36.1, 25.7; TLC R.sub.f0.3 (EtOAc/Hexane=1/10); HRMS (FI) Calcd for C.sub.9H.sub.8O: 132.0570, found: 132.0570.

[0100] CF.sub.3CH.sub.2OH (Trifluoroethanol): .sup.1H NMR (400 MHz, CDCl.sub.3) 3.92 (q, J=8.8 Hz, 2H), 3.21 (br, 1H, OH); .sup.19F NMR (470 MHz, CDCl.sub.3) 79.08 (s).

[0101] CF.sub.3CHO (Trifluoroacetaldehyde; b.p.18 C.): .sup.19F NMR (470 MHz, CDCl.sub.3) 84.62 (s)

##STR00065##

[0102] .sup.1H NMR (CDCl.sub.3, 500 MHz) 3.98 (sept, J=6.5 Hz, 1H), 3.17 (s, 1H, OH), 1.38 (d, J=6.5 Hz, 3H); .sup.19F NMR (470 MHz, CDCl.sub.3) 81.4 (s).

##STR00066##

[0103] .sup.1H NMR (CDCl.sub.3, 500 MHz) 2.48 (s, 3H); .sup.19F NMR (470 MHz, CDCl.sub.3) 80.0 (s).

[0104] 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.