Kinetic resolution method for asymmetric catalytic hydrogenation of racemic beta-aryl ester or lactone

Abstract

The invention provides a kinetic resolution method for asymmetric catalytic hydrogenation of racemic beta-aryl ester or lactone. Specifically, the invention provides a kinetic resolution method for asymmetric catalytic hydrogenation of racemic beta-aryl ester or lactone containing aryl, alkenyl, alkynyl and alkyl, and chiral gamma-aryl primary alcohol is prepared. According to the method, a chiral Ir-SpiroPAP catalyst or an enantiomer thereof is adopted, and the conversion number of the chiral Ir-SpiroPAP catalyst is as high as 600. In the imgabs0 #, R can be aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkyl or cyclic alkyl; r2 is alkyl; x can be hydrogen, alkyl, alkoxy, halogen or carboxylic ester group; wherein the structural formula of the Ir-SpiroPAP catalyst is # imgabs 1 # or an enantiomer thereof, and Y is hydrogen or alkyl.

Description

Technical Field

[0001] The present invention relates to the technical field of asymmetric synthesis, in particular to a kinetic resolution method for asymmetric catalytic hydrogenation of racemic beta-aryl esters or lactones. Background Art

[0002] Asymmetric hydrogenation of racemic esters using chiral catalysts has emerged as a promising strategy for the synthesis of chiral primary alcohols. Current successes primarily involve the asymmetric hydrogenation of racemic α-substituted esters, yielding β-chiral primary alcohols via dynamic kinetic analysis. There is only one reported case of asymmetric hydrogenation, the asymmetric hydrogenation of a racemic ester (patent document CN104355997 B), which enantioselectively synthesized a chiral primary alcohol with a distal stereocenter from the δ position via kinetic analysis.

[0003] This patent document (CN104355997 B) demonstrates the remarkable efficacy of chiral Ir-SpiroPAP catalyst in catalyzing the asymmetric hydrogenation of racemic δ-hydroxy esters through kinetic analysis, thereby achieving the enantioselective synthesis of chiral 1,5-diols and recovering the chiral δ-hydroxy esters with excellent enantioselectivity.

[0004]

[0005] However, the development of efficient catalytic protocols for the kinetically resolved asymmetric hydrogenation of racemic esters containing distant stereocenters has been hampered by the low hydrogenation reactivity of esters and the inherent complexity of resolving distant stereocenters. Kinetically resolved asymmetric hydrogenation of racemic esters containing distant stereocenters remains a formidable challenge.

[0006] To address this issue, the present invention provides an asymmetric hydrogenation reaction for racemic β-aryl esters or lactones containing a remote benzyl tertiary stereocenter. In the presence of a chiral Ir-SpiroPAP catalyst, a hydroxyl group is introduced into the racemic β-aryl ester or lactone, followed by hydrogenation, and enhanced chiral recognition through the lactone form. Summary of the Invention

[0007] The invention provides a highly efficient kinetic resolution method for asymmetric catalytic hydrogenation of racemic beta-aryl esters or lactones, and selectively synthesizes chiral gamma-aryl primary alcohols.

[0008] In order to achieve the technical purpose of the present invention, the technical solution of the present invention is:

[0009] First, the present invention provides a chiral γ-aryl primary alcohol and carboxylate compound or its enantiomer, the structural formula of which is:

[0010]

[0011] Wherein, R can be aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkyl or cyclic alkyl; R 1 It can be an aryl group or a substituted aryl group; X 1 , X 2 They may be identical or different hydrogen, alkyl, alkoxy, halogen or carboxylate.

[0012] The aryl group is preferably phenyl, thiophene, furan or pyridine; the substituted aryl group is preferably substituted phenyl; the substituted phenyl group is preferably toluene, halobenzene, anisole, phenylpropyl ether;

[0013] The substituted alkenyl group is wherein D is hydrogen, alkyl, alkoxy or halogen;

[0014] The substituted alkynyl group is preferably an alkyl group, a cyclic alkyl group, a phenyl group, a thiophene group or wherein D is hydrogen, alkyl, alkoxy or halogen;

[0015] Most preferably, the chiral γ-aryl primary alcohol compound has the structural formula:

[0016]

[0017] The present invention provides racemic β-aryl ester or lactone compounds for preparing compounds of formula A and formula B, preferably having the structural formula:

[0018]

[0019]

[0020] In a second aspect, the present invention provides a kinetic resolution method for asymmetric catalytic hydrogenation of racemic β-aryl esters or lactones, comprising asymmetric catalytic hydrogenation of the racemic β-aryl esters or lactones in the presence of an iridium catalyst containing a chiral spirocyclic pyridine aminophosphine ligand and a base to prepare a chiral β-aryl ester and the corresponding chiral γ-aryl primary alcohol:

[0021]

[0022] The racemic β-aryl ester or lactone is preferably a lactone compound, specifically

[0023] X may be hydrogen, alkyl, alkoxy, halogen, or carboxylate.

[0024] Wherein, R can be aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkyl or cyclic alkyl; R 2 It is an alkyl group.

[0025] The asymmetric hydrogenation reaction process of the lactone compound is:

[0026]

[0027]

[0028] Here, X can be hydrogen, alkyl, alkoxy, halogen or carboxylate.

[0029] Preferably, the reaction formula of the asymmetric catalytic hydrogenation is:

[0030]

[0031] The prepared (R)-3 compound and (S)-2 compound are not disclosed in the prior art.

[0032]

[0033] The prepared (R)-10 compound is not disclosed in the prior art.

[0034]

[0035] The prepared (R)-12 compound is not disclosed in the prior art.

[0036]

[0037] Wherein, the chiral spirocyclic pyridine aminophosphine ligand iridium catalyst structural formula is:

[0038]

[0039] or an enantiomer thereof, wherein Y may be hydrogen or alkyl.

[0040] (R)-4e is preferably:

[0041]

[0042] Or it is the enantiomer (S)-4e catalyst. When the catalyst is (S)-4e, the asymmetric catalytic hydrogenation reaction formula can be:

[0043] The definition of R is the same as above.

[0044] When the catalyst is (S)-4e, the asymmetric catalytic hydrogenation reaction formula can also be:

[0045]

[0046]

[0047] The above-mentioned asymmetric catalytic hydrogenation reaction is carried out in the presence of a base, wherein the base is an alkali metal salt of an alcohol (such as potassium tert-butoxide, sodium tert-butoxide, potassium isopropoxide, sodium isopropoxide), an alkali metal hydroxide (such as potassium hydroxide, sodium hydroxide), or an alkali metal carbonate (such as potassium carbonate, sodium carbonate), preferably an alkali metal salt of an alcohol.

[0048] The above-mentioned asymmetric catalytic hydrogenation reaction is carried out in the presence of a solvent, wherein the reaction solvent is one of methanol, ethanol, propanol, isopropanol, butanol, tetrahydrofuran, toluene, methyl tert-butyl ether, dioxane, DMF, DMSO or a mixed solvent thereof, preferably an alcohol solvent.

[0049] The asymmetric hydrogenation method provided by the present invention has significant technical benefits for racemic β-aryl esters or lactones containing aryl, alkenyl, alkynyl, and alkyl groups. It enables the selective synthesis of chiral γ-aryl primary alcohols using kinetic analysis, with very high turnover numbers exceeding 600. These compounds serve as basic raw materials for the synthesis of various bioactive chiral compounds and have extremely high industrial value. DETAILED DESCRIPTION

[0050] To further understand the present invention, the asymmetric hydrogenation of β-aryl esters provided by the present invention is described in detail below with reference to the examples. It should be understood that these examples are only intended to further illustrate the features of the present invention and are not intended to limit the scope of the present invention or the scope of the claims.

[0051] Example 1:

[0052]

[0053] The racemic substrate rac-1a (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2a (yield 45%, 87.5% ee) and (R)-3a (yield 46%, 91.1% ee). Characterization data of (S)-2a: colorless oil, 115 mg, 45% yield, 87.5% ee. 1H NMR(400MHz, CDCl3)δ:7.34-7.24(m,5H),7.23-7.18(m,1H),7.13-7.00(m,2H),6.85(dd,J =14.0,7.9Hz,2H),6.05(s,1H),4.86(t,J=7.8Hz,1H),3.64(s,3H),3.14(d,J=7.8Hz,3H). 13 C NMR (100MHz, CDCl3) δ: 174.0, 153.5, 143.0, 130.4, 128.6, 128.3, 127.9, 127.8, 126.6, 120.9, 120.9, 116.8, 116.8, 52.2, 39.9, 39.7. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 10.31 min; t R (R) = 16.97 min. Characterization data of (R)-3a: white solid, mp 81-82 ° C, 105 mg, 46% yield, 91.1% ee. 1 H NMR(400MHz, CDCl3)δ:7.36-7.28(m,4H),7.25-7.19(m,1H),7.07(dd,J=7.6,1.6Hz,1H),7.00(dd,J=7.6,1.6Hz,1H),6.86-6.8 2(m,1H),6.34(s,1H),4.59(dd,J=9.8,6.0Hz,1H),3.80-3.75(m,1H),3.58-3.52(m,1H),2.43-2.35(m,1H),2.22-2.14(m,1H). 13 C NMR(100MHz, CDCl3)δ:153.7,144.1,131.0,128.8,128.5,128.4,128.3,128.3,127.4,126.3,121.0,116.0,60.8,38.7,37.1., (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 16.94 min; tR (R)=20.29min.HRMS(ESI)Calcd for C 15 H 16 NaO2([M+Na] + ):251.1043,Found:251.1041.

[0054] Example 2:

[0055] Aryl and substituted aryl substrate structures (1b to 1r) and reaction equations:

[0056]

[0057] The racemic substrate rac-1b (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2b (yield 43%, 87.4% ee) and (R)-3b (yield 49%, 91.1% ee). Characterization data of (S)-2b: Colorless oil, 114 mg, 43% yield, 87.4% ee. 1 H NMR(400MHz, CDCl3)δ:7.26(d,J=3.8Hz,4H),7.23-7.12(m,1H),6.87-6.80(m,2H),6.67(d,J=7 .8Hz,1H),6.20(s,1H),4.85(t,J=7.8Hz,1H),3.59(s,3H),3.11(d,J=7.8Hz,2H),2.18(s,3H). 13 C NMR (100MHz, CDCl3) δ: 173.9, 151.2, 143.0, 130.0, 129.7, 128.7, 128.4, 128.1, 127.8, 126.4, 116.4, 51.9, 40.0, 39.5, 20.6. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 85:15; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (R) = 15.77 min; t R (S)=18.25min.HRMS(ESI)Calcd for C 17 H 19 O3([M+H] + ):271.1329,Found:271.1324. Characterization data of (R)-3b: white solid, mp 118-120 ° C, 119 mg, 49% yield, 91.1% ee. 1 HNMR(400MHz, CDCl3)δ:7.34-7.26(m,4H),7.23-7.17(m,1H),6.87-6.80(m,1H),6.78-6.64(m,3H),4.59-4.55 (m,1H),3.87-3.67(m,1H),3.62-3.33(m,1H),2.78(s,1H),2.39-2.31(m,1H),2.16(s,3H),2.15-2.03(m,1H). 13 C NMR (100MHz, CDCl3) δ: 151.6, 144.2, 130.6, 130.3, 129.3, 128.6, 128.4, 128.0, 126.4, 116.1, 60.8, 38.8, 37.1, 20.8. 60.3(c 1.0,MeOH)[lit. 13 (c 1.0, MeOH)]. HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 10.87 min; t R (S)=17.88min.HRMS(ESI)Calcd for C 16 H 19 O2([M+H] + ):243.1380,Found:243.1374.

[0058] Example 3:

[0059] The racemic substrate rac-1c (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2c (yield 45%, 89.1% ee) and (R)-3c (yield 48%, 85.3% ee). Characterization data of (S)-2c: colorless oil, 129 mg, 45% yield, 89.1% ee. 1 H NMR (400MHz, CDCl3) δ: 7.25 (m, 4H), 7.17 (t, J = 6.6Hz, 1H), 6.73 (d, J = 8.4Hz, 1H), 6.66-6.45 (m,1H),5.93(s,1H),4.82(t,J=7.8Hz,1H),3.65(s,3H),3.60(s,3H),3.09(d,J=7.7Hz,2H). 13 C NMR (100MHz, CDCl3) δ: 153.9, 147.8, 143.9, 132.3, 128.5, 128.3, 126.4, 116.8, 114.9, 111.9, 60.7, 55.7, 39.0, 37.1. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 8.67 min; t R (S)=10.02min.HRMS(ESI)Calcd for C 16 H 19 O2([M+H] + ):287.1278,Found:287.1271. Characterization data of (R)-3c: white solid, mp 104-105 ° C. 124 mg, 48% yield, 85.3% ee. 1HNMR (400MHz, CDCl3) δ: 7.30 (d, J = 4.1Hz, 4H), 7.24-7.18 (dt, J = 8.6, 4.0Hz, 1H), 6.78 (d, J = 8.7Hz, 1H), 6.63 (dd, J = 8.7, 3.0Hz, 1H), 6.56 (d, J = 2.9Hz, 1H),5.90(s,1H),4.56(dd,J=10.0,5.9Hz,1H),3.78-3.36(m,1H),3.67(s, 3H),3.56-3.49(m,1H),2.40-2.32(m,1H),2.20-2.12(m,1H),1.99(s,1H). 13 C NMR (100MHz, CDCl3) δ: 153.9, 147.8, 143.9, 132.3, 128.5, 128.3, 126.4, 116.8, 114.9, 111.9, 60.7, 55.7, 39.0, 37.1. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 10.36 min; t R (R)=12.84min.HRMS(ESI)Calcd for C 16 H 19 O3([M+H] + ):259.1329,Found:259.1321.

[0060] Example 4:

[0061] The racemic substrate rac-1d (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2d (yield 47%, 83.7% ee) and (R)-3d (yield 47%, 87.1% ee). Characterization data of (S)-2d: colorless oil, 137 mg, 47% yield, 83.7% ee. 1 H NMR(400MHz, CDCl3)δ:7.39-7.27(m,3H),7.27-7.18(m,3H),7.07-6.91(m,2H),6.74(dd, J=8.5,5.0Hz,1H),6.58(s,1H),4.84(t,J=7.8Hz,1H),3.64(s,3H),3.11(d,J=8.0Hz,2H). 13 C NMR (100MHz, CDCl3) δ: 174.0, 152.2, 142.1, 132.4, 128.7, 128.2, 127.8, 127.7, 126.9, 125.7, 118.3, 52.3, 39.6, 39.5. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); nhexane / 2-propanol = 94:6; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 16.59 min; t R (R)=19.31min.HRMS(ESI)Calcd for C 16 H 16 ClO3([M+H] + ):291.0782,Found:291.0771. Characterization data of (R)-3d: white solid, mp 122-123 ° C. 121 mg, 46% yield, 87.1% ee. 1H NMR(400MHz, CDCl3)δ:7.40-7.17(m,4H),7.03(dd,J=8.6,2.6Hz,1H),6.92(d,J=2.6Hz,1H),6.78(d,J=8.6Hz,1H), 4.55(dd,J=9.8,6.0Hz,1H),3.80(dt,J=10.3,5.0Hz,1H),3.57-3.50(m,1H),2.42-2.33(m,1H),2.19-2.11(m,1H). 13 C NMR (100MHz, CDCl3) δ: 152.7, 143.1, 132.8, 128.8, 128.6, 128.3, 127.5, 126.9, 126.0, 118.0, 60.7, 38.9, 36.8. (c 1, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 9.00 min; t R (R)=9.66min.HRMS(ESI)Calcdfor C 15 H 15 ClNaO2([M+Na] + ):285.0653,Found:285.0651.

[0062] Example 5:

[0063] The racemic substrate rac-1e (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2e (yield 47%, 83.7% ee) and (R)-3e (yield 47%, 87.1% ee). Characterization data of (S)-2e: white solid, mp 125-126°C. 154 mg, 49% yield, 93.7% ee. 1H NMR(400MHz, CDCl3)δ:7.81-7.78(m,2H),7.32-7.28(m,2H),7.24-7.20(m,1H),6.84(dd,J=8.2,1. 6Hz,1H),6.69(d,J=8.5Hz,1H),4.85(t,J=7.7Hz,1H),3.84(s,1H),3.65(s,2H),3.22-3.13(m,2H). 13 C NMR (100MHz, CDCl3) δ: 173.9, 167.3, 158.2, 142.4, 130.4, 130.2, 130.0, 128.8, 127.9, 126.9, 122.6, 116.6, 52.3, 52.1, 39.8, 39.6. (c 1, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (S) = 9.09 min; t R (R)=10.66min.HRMS(ESI)Calcd for C 18 H 19 O5([M+H] + ):315.1227, Found:315.1221. Characterization data of (R)-3e: white solid, mp 120-121 ° C. 143 mg, 50% yield, 84.7% ee. 1 H NMR (400MHz, CDCl3) δ: 8.16 (s, 1H), 7.78 (d, J = 2.2Hz, 1H), 7.71 (dd, J = 8.4, 2.2Hz, 1H), 7.25-7.20 (m, 4H), 7.17-7.13 (m, 1H), 6.79 (d, J =8.5Hz,1H),4.58(t,J=7.8,1H),3.80(s,3H),3.68-3.63(m,1H),3.56-3.50(m,1H),2.91(s,1H),2.38-2.28(m,1H),2.24-2.16(m,1H). 13 C NMR (100MHz, CDCl3) δ:167.8,158.8,143.4,131.1,130.5,129.7,128.6,128.3,126.6,122.2,115.9,60.8,52.1,39.0,37.1., (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (S) = 8.15 min; t R (R)=9.89min.HRMS(ESI)Calcdfor C 17 H 19 O4([M+H] + ):287.1278,Found:287.1269.

[0064] Example 6:

[0065] The racemic substrate rac-1f (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2f (yield 47%, 91.2% ee) and (R)-3f (yield 50%, 88.0% ee). Characterization data of (S)-2f: colorless oil, 127 mg, 47% yield; 91.2% ee. 1 H NMR(400MHz, CDCl3)δ:7.34-7.22(m,4H),7.22-7.12(m,1H),6.91(d,J=7.8Hz,1H),6.66(d,J=8.0Hz,1H),6 .62(s,1H),6.12(d,J=14.6Hz,1H),4.82(t,J=7.6Hz,1H),3.61(s,3H),3.11(d,J=7.6Hz,2H),2.22(s,3H). 13 C NMR (100MHz, CDCl3) δ: 174.1, 153.3, 143.2, 137.8, 128.6, 128.1, 127.9, 127.5, 126.6, 121.7, 117.5, 52.1, 39.7, 21.0. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 85:15; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (R) = 10.07 min; t R (S)=11.45min.HRMS(ESI)Calcd for C 17 H 19 O3([M+H] + ):271.1329, Found:271.1324(R)-3f characterization data: white solid, mp 87-88 ° C, 121 mg, 50% yield, 88.0% ee. 1 H NMR(400MHz, CDCl3)δ:7.46-7.56(m,1H),7.28-7.20(m,4H),7.16-7.13(m,1H),6.82(d,J=7.8Hz,1H),6.65-6.40( m,2H),4.58-4.52(m,1H),3.70-3.61(m,1H),3.54-3.44(m,2H),2.39-2.25(m,1H),2.16(s,3H),2.13-2.00(m,1H). 13 C NMR (100MHz, CDCl3) δ: 152.3, 144.1, 130.4, 129.0, 128.6, 128.3, 126.5, 126.4, 124.8, 120.7, 60.8, 39.3, 37.1, 16.4. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); nhexane / 2-propanol = 85:15; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 18.96 min; t R (S)=26.18min.HRMS(ESI)Calcd for C 16 H 19 O2([M+H] + ):243.1380,Found:243.1373.

[0066] Example 7:

[0067] The racemic substrate rac-1g (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford the products (S)-2g (yield 51%, 86.8% ee) and (R)-3g (yield 48%, 89.1% ee). Characterization data of (S)-2g: colorless oil, 137 mg, 51% yield, 86.8% ee. 1 H NMR(400MHz, CDCl3)δ:7.32-7.27(m,2H),7.26-7.16(m,3H),6.90(d,J=9.2Hz,1H),6.43-6.40( m,2H),6.26(s,1H),4.76(dd,J=8.8,6.5Hz,1H),3.73(s,3H),3.65(s,3H),3.11(d,J=7.6,2H). 13 C NMR (100MHz, CDCl3) δ: 159.1, 154.9, 144.4, 129.4, 128.7, 128.6, 128.3, 126.4, 123.2, 106.8, 102.4, 60.9, 55.4, 38.5, 37.1. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (R) = 4.00 min; t R (S)=4.63min.HRMS(ESI)Calcd for C 17 H 19 O4([M+H] + ):287.3345,Found:287.3340.(R)-3g characterization data: white solid, mp 89-90 ° C, 124 mg, 48% yield, 89.1% ee. 1H NMR(400MHz, CDCl3)δ:7.34-7.27(m,4H),7.23-7.19(m,1H),6.86(d,J=8.3Hz,1H),6.47-6.36(m,2H),6.23(s,1H),4.47(dd,J=1 0.1,5.7Hz,1H),3.80(dt,J=10.0,4.8Hz,1H),3.74(s,3H),3.60-3.53(m,1H),2.41-2.33(m,1H),2.19-2.12(m,1H),1.77(s,1H). 13 C NMR (100MHz,CDCl3)δ: 1 157.9,153.7,136.1,131.2,129.2,128.7,127.3,121.0,116.0,113.8,60.7,55.3,37.9,37.3. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (R) = 4.63 min; t R (S)=6.22min.HRMS(ESI)Calcd for C 16 H 19 O3([M+H] + ):259.3245,Found:259.3241.

[0068] Example 8:

[0069] The racemic substrate rac-1h (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2h (yield 45%, 88.2% ee) and (R)-3h (yield 47%, 90.6% ee). Characterization data of (S)-2h: colorless oil, 121 mg, 45% yield, 88.2% ee. 1 H NMR(400MHz, CDCl3)δ:7.26(d,J=6.5Hz,4H),7.22-7.12(m,1H),6.91(d,J=7.8Hz,1H),6.66(d,J=7.9Hz,1H) ,6.62(s,1H),6.12(d,J=14.8Hz,1H),4.82(t,J=7.8Hz,1H),3.61(s,3H),3.11(d,J=7.6Hz,2H),2.22(s,3H). 13 C NMR (100MHz, CDCl3) δ: 174.1, 153.3, 143.2, 137.8, 128.6, 128.1, 127.9, 127.5, 126.6, 121.7, 117.5, 52.1, 39.7, 21.0. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (R) = 9.19 min; t R (S)=10.75min.HRMS(ESI)Calcd for C 16 H 19 O3([M+H] + ):271.1329,Found:271.1325. Characterization data of (R)-3h: white solid, mp 67-68 ° C, 114 mg, 47% yield, 90.6% ee. 1H NMR(400MHz, CDCl3)δ:7.31-7.29(m,4H),7.23-7.16(m,1H),6.98(d,J=7.2Hz,1H),6.86(d,J=7.5Hz,1H),6.76(t,J=7.5Hz,1H),6.01(s,1H),4 .56(dd,J=9.6,6.1Hz,1H),3.78(dt,J=10.4,5.1Hz,1H),3.55(td,J=10 .3,9.8,4.5Hz,1H),2.41-2.35(m,1H),2.25(s,3H),2.32-2.15(m,1H). 13 C NMR(100MHz, CDCl3)δ:152.3,144.1,130.4,129.0,128.6,128.3,126.5,126.4,124.8,120.7,60.8,39.3,37.1,16.4., (c1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (S) = 9.07 min; t R (R)=9.75min.HRMS(ESI)Calcd for C 16 H 19 O2([M+H] + ):243.1380,Found:243.1381.

[0070] Example 9:

[0071] The racemic substrate rac-1i (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2i (yield 44%, 98.2% ee) and (R)-3i (yield 50%, 80.7% ee). Characterization data of (S)-2i: Colorless oil, 125 mg, 44% yield, 98.2% ee. 1 H NMR (400MHz, CDCl3) δ: 7.14-7.05 (m, 3H), 7.04-6.98 (m, 1H), 6.88 (d, J = 8.4Hz, 1H), 6.7 8(s,1H),4.28-4.21(m,1H),3.80(s,3H),3.18-2.68(m,2H),2.26(s,3H),1.54(s,3H). 13 C NMR(100MHz, CDCl3)δ:167.8,158.8,149.4,134.1,132.3,129.0,128.4,125.6,116.7,114.3,55.1,39.8,37.2,20.6., (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 93:7; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (R) = 17.19 min; t R (S)=20.15min.HRMS(ESI)Calcd for C 18 H 21 O3([M+H] + ):285.1485,Found:285.1481. Characterization data of (R)-3i: white solid, 128 mg, 50% yield, 80.7% ee. 1H NMR(400MHz, CDCl3)δ:7.24-7.14(m,2H),6.94-6.82(m,3H),6.77(s,1H),6.71(d,J=8.1Hz,1H),4.63- 4.37(m,1H),3.90-3.66(m,4H),3.60-3.46(m,1H),2.42-2.28(m,1H),2.18(s,3H),2.16-1.87(m,1H). 13 C NMR (100MHz, CDCl3) δ: 157.8, 151.3, 135.9, 130.6, 130.0, 129.0, 128.9, 127.6, 115.9, 113.7, 60.6, 55.1, 37.8, 37.0, 20.5. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 93:7; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (S) = 14.82 min; t R (R)=16.12min.HRMS(ESI)Calcd for C 17 H 21 O2([M+H] + ):257.1536,Found:257.1534.

[0072] Example 10:

[0073] The racemic substrate rac-1j (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times, then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2j (yield 50%, 89.2% ee) and (R)-3j (yield 48%, 99.5% ee). Characterization data of (S)-2j: white solid, mp 80-82 °C, 126 mg, 50% yield, 89.2% ee. 414 mg, 82% yield.1 H NMR(400MHz, CDCl3)δ:7.30-7.25(m,2H),7.24-7.19(m,1H),7.10(d,J=7.6Hz,1H),7.08-7.00(m ,2H),6.90(d,J=7.6Hz,1H),4.39(t,J=4.5Hz,1H),3.09-3.00(m,2H),2.35(s,3H),2.15(s,3H). 13 C NMR (100MHz, CDCl3) δ: 167.5, 150.5, 140.5, 134.2, 130.5, 129.2, 127.5, 127.1, 126.0, 124.2, 123.1, 38.5, 37.7, 18.7, 15.9. (c1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 93:7; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (R) = 11.20 min; t R (S) = 14.67 min. Characterization data of (R)-3j: white solid, mp 130-132 ° C. 123 mg, 48% yield, 99.5% ee. 1 H NMR(400MHz, CDCl3)δ:7.35-7.26(m,4H),7.24-7.16(m,1H),6.92(d,J=7.6Hz,1H),6.66(d,J=7.6Hz,1H),4.82-4 .73(m,1H),3.88-3.67(m,1H),3.56-3.48(m,1H),2.64-2.52(m,1H),2.47-2.28(m,1H),2.18(s,6H),1.63(s,1H). 13 C NMR (100MHz, CDCl3) δ: 153.0, 143.7, 135.9, 129.0, 128.6, 128.5, 127.5, 126.2, 123.4, 123.0, 61.3, 38.1, 33.4, 20.8, 16.2. (c 1.0, CHCl3). HPLC conditions: Chiralcel AS-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 29.22 min; t R(R)=39.38min.HRMS(ESI)Calcdfor C 17 H 21 O2([M+H] + ):257.1536,Found:257.1534.

[0074] Example 11:

[0075] The racemic substrate rac-1k (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2k (yield 53%, 83.2% ee) and (R)-3k (yield 45%, 95.7% ee). Characterization data of (S)-2k: Colorless oil, 143 mg, 53% yield, 83.2% ee. 1 H NMR(400MHz, CDCl3)δ:7.14(d,J=7.9Hz,2H),7.12-6.99(m,4H),6.83(t,J=7.4Hz,1H),6.76(d, J=8.1Hz,1H),6.27(s,1H),4.84(t,J=7.6Hz,1H),3.60(s,3H),3.22-3.00(m,1H),2.28(s,3H). 13 C NMR (100MHz, CDCl3) δ: 173.9, 151.2, 143.1, 130.5, 130.4, 129.0, 128.7, 128.4, 127.9, 126.7, 117.1, 52.2, 39.8, 39.7, 20.9. (c 1.0, MeOH). HPLC conditions: Chiralcel OD-3 column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 5.72 min; t R(S)=7.63min.HRMS(ESI)Calcd for C 17 H 19 O3([M+H] + ):271.1329,Found:271.1324. Characterization data of (R)-3k: white solid, mp 91-92 ° C.109 mg, 45% yield, 95.7% ee. 1 H NMR (400MHz, CDCl3) δ: 7.19 (d, J = 8.0Hz, 2H), 7.12 (d, J = 8.0Hz, 2H), 7.09-7.03 (m, 1H), 7.00 (d, J = 7.6Hz, 1H), 6.83 (dd, J = 13.6, 7.6Hz, 2H), 6. 72(s,1H),4.56(dd,J=9.7,6.1Hz,1H),3.78-3.75(m,1H),3.58-3.52( m,1H),2.54(s,1H),2.41-2.34(m,1H),2.34(s,3H),2.20-2.12(m,1H). 13 C NMR (100MHz, CDCl3) δ: 153.8, 141.0, 135.9, 131.1, 129.2, 128.8, 128.2, 127.4, 121.1, 116.1, 60.8, 38.4, 37.2, 21.1. (c 1.0, MeOH). HPLC conditions: Chiralcel OD-3 column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 8.96 min; t R (R)=11.75min.HRMS(ESI)Calcd for C 16 H 19 O2([M+H] + ):243.1380,Found:243.1380.

[0076] Example 12:

[0077] The racemic substrate rac-1l (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times, then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2l (yield 45%, 90.5% ee) and (R)-3l (yield 50%, 84.3% ee). Characterization data of (S)-2l: colorless oil, 129 mg, 45% yield, 90.5% ee. 1 H NMR(400MHz, CDCl3)δ:7.21-7.15(m,2H),7.12-7.02(m,2H),6.90-6.79(m,4H), 6.11(s,1H),4.82(t,J=7.8Hz,1H),3.77(s,3H),3.63(s,3H),3.18-3.03(m,2H). 13 C NMR (100MHz, CDCl3) δ: 173.9, 158.1, 153.5, 135.0, 130.6, 128.9, 128.1, 127.6, 120.7, 116.5, 113.9, 55.2, 52.0, 39.8, 39.4. (c1.0, MeOH). HPLC conditions: Chiralcel OD-3 column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 8.99 min; t R (S)=9.68min.HRMS(ESI)Calcd for C 17 H 19 O4([M+H] + ):287.1278,Found:287.1278. Characterization data of (R)-3l: white solid, mp 98-99 ° C.129 mg, 50% yield, 84.3% ee. 1H NMR(400MHz, CDCl3)δ:7.20(d,J=8.6Hz,2H),7.07-7.02(m,1H),6.97(d,J=7.5Hz,1H),6.88-6.76(m,5H),4.54(dd, J=9.7,6.1Hz,1H),3.77(s,4H),3.74-3.72(m,1H),3.55-3.50(m,1H),2.64(s,1H),2.38-2.28(m,1H),2.13(m,1H). 13 C NMR (100MHz, CDCl3) δ: 157.9, 153.7, 136.2, 131.3, 129.2, 128.7, 127.3, 121.0, 116.0, 113.9, 60.8, 55.3, 37.9, 37.3. (c 1.0, CHCl3). HPLC conditions: Chiralcel OD-3 column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 19.48 min; t R (S)=11.40min.HRMS(ESI)Calcd for C 16 H 22 NO3([M+NH4] + ):276.1594,Found:276.1586.

[0078] Example 13:

[0079] The racemic substrate rac-1m (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2m (yield 47%, 94.7% ee) and (R)-3m (yield 50%, 91.0% ee). Characterization data of (S)-2m: colorless oil, 47% yield, 94.7% ee. 1H NMR(400MHz, CDCl3)δ:7.26-7.24(m,2H),7.20-7.18(m,2H),7.16-7.07(m,1H),7.01(dd,J=7.8,1. 7Hz,1H),6.94-6.75(m,2H),5.80(s,1H),4.84(t,J=7.7Hz,1H),3.63(s,3H),3.10(d,J=7.7Hz,2H). 13 C NMR (100MHz, CDCl3) δ: 173.6, 153.4, 141.6, 132.4, 130.1, 129.4, 128.7, 128.3, 128.1, 121.3, 117.0, 100.1, 52.2, 39.6, 39.4. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 93:7; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (S) = 12.55 min; t R (R)=19.69min.HRMS(ESI)Calcd for C 16 H 16 ClO3([M+H] + ):291.0782,Found:291.0779. Characterization data of (R)-3m: white solid, mp 102-103 ° C, 131 mg, 50% yield, 91.0% ee. 1 H NMR (400MHz, CDCl3) δ: 7.23 (q, J = 8.4Hz, 4H), 7.07 (t, J = 7.7Hz, 1H), 6.94-6.93 (m, 1H), 6.86-6.80 (m, 2H), 6.68 (s, 1H), 4.58 (d d,J=10.0,5.9Hz,1H),3.75(dt,J=10.5,5.0Hz,1H),3.53(td,J=10.0,4.3Hz,1H),2.51(s,1H),2.38-2.29(m,1H),2.13(m,1H). 13 CNMR(100MHz, CDCl3)δ:153.8,142.7,132.1,130.4,129.7,128.8,128.6,127.7,121.4,116.3,60.7,38.2,37.0. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 5.87 min; t R (S)=8.04min.HRMS(ESI)Calcd for C 17 H 21 O2([M+H] + ):263.0833,Found:263.0829.

[0080] Example 14:

[0081] The racemic substrate rac-1n (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (R)-2n (yield 50%, 90.5% ee) and (S)-3n (yield 47%, 97.0% ee). Characterization data of (R)-2n: colorless oil, 143 mg, 50% yield, 90.5% ee. 1 H NMR (400MHz, CDCl3) δ7.24 (dd, J=7.5, 1.7Hz, 1H), 7.21-7.12 (m, 2H), 7.06 (td, J=7.5, 1.7Hz, 1H), 6.93 (td ,J=7.5,1.1Hz,1H),6.86-6.81(m,4H),5.11(t,J=7.8Hz,1H),3.85(s,3H),3.58(s,3H),3.19-3.08(m,2H). 13 C NMR (100MHz, CDCl3) δ173.0,155.9,154.0,131.1,129.4,127.9,127.8,127.4,127.1,121.5,120.8,117.0,111.2,56.0,52.0,39.0,32.3. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 4.62 min; t R (S)=5.42min.HRMS(ESI)Calcd forC 17 H 19 O4([M+H] + ):287.1278,Found:287.1273. Characterization data of (S)-3n: white solid, mp 105-106 ° C, 121 mg, 47% yield, 97.0% ee. 1 H NMR (400MHz, CDCl3) δ7.28 (dd, J=7.6, 1.7Hz, 1H), 7.20-7.13 (m, 2H), 7.04 (td, J=7.7, 1.7Hz, 1H), 6.95 (td, J= 7.6,1.2Hz,1H),6.88-6.78(m,3H),4.77(t,J=7.8Hz,1H),3.79(s,3H),3.63-3.50(m,2H),2.32-2.24(m,2H). 13 C NMR (101MHz, CDCl3) δ156.1,154.2,132.1,130.2,127.7,127.6,127.4,127.3,121.6,120.8,116.4,111.0,60.8,56.0,36.8,31.5. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 39.65 min; t R (S)=42.12min.HRMS(ESI)Calcd for C 16 H 19 O3([M+H] + ):259.1329,Found:259.1327.

[0082] Example 15:

[0083] The racemic substrate rac-1o (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2o (yield 46%, 96.3% ee) and (R)-3o (yield 51%, 86.6% ee). Characterization data of (S)-2o: colorless oil, 138 mg, 46% yield, 96.3% ee. 1 H NMR (400MHz, CDCl3) δ: 7.17 (d, J = 8.6 Hz, 2H), 6.91-6.79 (m, 4H), 6.73 (d, J = 8.1 Hz, 1H), 5.71 (s,1H),4.75(t,J=7.7Hz,1H),3.78(s,3H),3.63(s,3H),3.08(d,J=7.7Hz,2H),2.20(s,3H). 13 C NMR (100MHz, CDCl3) δ: 173.9, 158.3, 151.1, 135.1, 130.7, 130.4, 128.9, 128.8, 128.4, 117.2, 114.1, 55.4, 52.2, 40.1, 39.0, 20.9. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (S) = 9.55 min; t R (R)=17.87min.HRMS(ESI)Calcd for C 18 H 21 O4([M+H] + ):301.1434,Found:301.1429. Characterization data of (R)-3o: white solid, mp 105-106 ° C, 138 mg, 51% yield, 86.6% ee. 1HNMR(400MHz, CDCl3)δ:7.24-7.16(m,2H),6.90-6.81(m,3H),6.77(s,1H),6.73-6.70(m,1H),6.04(s,1H),4.48(dd,J=9.9,6 .2Hz,1H),3.79(s,3H),3.75-3.69(m,1H),3.56-3.50(m,1H),2.38-2.29(m,1H),2.19(s,3H),2.18-2.10(m,1H),2.06(s,1H). 13 C NMR (100MHz, CDCl3) δ: 158.1, 151.6, 136.2, 130.9, 130.3, 129.3, 129.2, 128.0, 116.2, 114.0, 60.9, 55.4, 38.1, 37.4, 20.9. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 19.91 min; t R (R)=22.74min.HRMS(ESI)Calcd for C 17 H 21 O3([M+H] + ):273.1485,Found:273.1480.

[0084] Example 16:

[0085] The racemic substrate rac-1p (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2p (yield 47%, 95.4% ee) and (R)-3p (yield 50%, 90.4% ee). Characterization data of (S)-2p: white solid, mp 113-114°C, 149 mg, 47% yield, 95.4% ee. 1 H NMR(400MHz, CDCl3)δ:7.22-7.12(m,2H),6.89-6.77(m,3H),6.69-6.54(m,2H),5.69(s, 1H), 4.77 (t, J = 7.7Hz, 1H), 3.77 (s, 3H), 3.69 (s, 3H), 3.64 (s, 3H), 3.08 (d, J = 7.7Hz, 2H). 13 C NMR (100MHz, CDCl3) δ: 173.9, 158.4, 154.0, 147.4, 134.8, 132.3, 128.9, 118.0, 114.4, 114.1, 112.2, 55.7, 55.3, 52.2, 40.0, 39.1. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 11.38 min; t R (R)=17.25min.HRMS(ESI)Calcd for C 18 H 21 O5([M+H] + ):317.1384,Found:317.1378. Characterization data of (R)-3p: white solid, mp 126-127 ° C, 144 mg, 50% yield, 90.4% ee. 1HNMR (400MHz, CDCl3) δ: 7.21 (d, J = 8.7Hz, 2H), 6.97-6.81 (m, 2H), 6.78 (d, J = 8.7Hz, 1H), 6.63 (dd, J = 8.7, 3.1Hz, 1H), 6.56 (d, J = 3.0Hz, 1H), 5.77 (s, 1H),4.49(dd,J=9.8,6.1Hz,1H),3.79(s,3H)3.77-3.74(m,1H),3.68(s,3 H),3.57-3.51(m,1H),2.37-2.29(m,1H),2.17-2.05(m,1H),1.62(s,1H). 13 C NMR (100MHz, CDCl3) δ: 158.2, 154.0, 147.8, 135.9, 132.6, 129.2, 117.0, 114.8, 114.0, 111.8, 60.8, 55.7, 55.4, 38.3, 37.2. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 10.16 min; t R (S) = 13.5 min.

[0086] Example 17:

[0087] The racemic substrate rac-1q (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-2q (yield 47%, 89.6% ee) and (R)-3q (yield 50%, 87.0% ee). Characterization data of (S)-2q: colorless oil, 162 mg, 47% yield, 89.6% ee. 1H NMR (400MHz, CDCl3) δ: 7.15 (d, J = 8.3Hz, 2H), 6.80 (dd, J = 13.1, 8.5Hz, 3H), 6.66-6.56 (m, 2H), 5.69 (s, 1H), 4.75 (t, J = 7.7 Hz,1H),3.88(t,J=6.5Hz,2H),3.69(s,3H),3.64(s,3H),3.07(d,J=7.7Hz,2H),1.82–1.74(m,2H),1.02(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ: 174.0, 158.0, 154.0, 147.4, 134.6, 132.4, 128.8, 118.1, 114.8, 114.4, 112.3, 69.6, 55.7, 52.2, 40.1, 39.1, 22.7, 10.7. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 210 nm UV detector; t R (R) = 16.69 min; t R (S) = 20.83 min. Characterization data of (R)-3q: colorless oil, 158 mg, 50% yield, 87.0% ee. 1 H NMR(400MHz, CDCl3)δ:7.22-7.14(m,2H),6.87-6.81(m,2H),6.77(d,J=8.7Hz,1H),6 .61(dd,J=8.7,3.1Hz,1H),6.55(d,J=3.1Hz,1H),6.06(s,1H),4.48(dd,J=9.8,6.1Hz ,1H),3.89(t,J=6.6Hz,2H),3.76(dd,J=10.6,5.1Hz,1H),3.67(s,3H),3.56-3.49(m ,1H),2.36-2.28(m,1H),2.16-2.08(m,2H),1.83-1.74(m,2H),1.02(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ: 157.8, 154.0, 147.9, 135.5, 132.5, 129.2, 117.2, 114.8, 114.7, 111.9, 69.6, 60.9, 55.7, 38.5, 37.2, 22.8, 10.7. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 9.66 min; t R (S)=17.72min.HRMS(ESI)Calcd for C 19 H 25 O4([M+H] + ):317.40455,Found:317.4041.

[0088] Example 18:

[0089] The racemic substrate rac-1r (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (R)-1r (yield 46%, 92.5% ee) and (S)-3r (yield 49%, 92.5% ee). Characterization data of (R)-1r: white solid, mp 125-126°C, 106 mg, 46% yield, 92.5% ee. 1 H NMR(400MHz, CDCl3)δ:7.34-7.30(m,1H),7.24-7.23(m,1H),7.19-7.09(m,3H),6.9 6-6.94(m,1H),6.81(d,J=3.5Hz,1H),4.61(t,J=6.1Hz,1H),3.14(d,J=6.1Hz,2H). 13 C NMR (100MHz, CDCl3) δ: 167.2, 151.4, 143.6, 129.3, 128.2, 127.3, 125.6, 125.4, 125.3, 124.9, 117.5, 37.6, 36.3. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 11.27 min; t R (S) = 12.68 min. Characterization data of (S)-3r: colorless oil, 115 mg, 49% yield, 92.5% ee. 1 H NMR(400MHz, CDCl3)δ:7.23-7.04(m,3H),7.04-6.74(m,4H),6.20(s,1H),4.82(dd,J=10.2,5.5Hz,1H),3.79( dt,J=10.9,4.8Hz,1H),3.53(ddd,J=10.9,9.6,4.1Hz,1H),2.54-2.46(m,1H),2.20-2.12(m,1H),1.97(s,1H). 13 C NMR (100MHz, CDCl3) δ: 153.7, 148.4, 130.2, 128.9, 128.1, 126.7, 124.5, 124.1, 121.5, 116.8, 60.6, 38.7, 35.1. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 17.51 min; t R (S)=23.87min.HRMS(ESI)Calcdfor C 13 H 15 O2S([M+H] + ):235.3205,Found:235.3201.

[0090] Example 19:

[0091] Alkenyl and substituted alkenyl substrate structures (substrates 9a to 9l) and reaction equations:

[0092]

[0093] The racemic substrate rac-9a (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9a (50% yield, 88.1% ee) and (R)-10a (49% yield, 88.7% ee). Characterization data of (S)-9a: white solid, mp 78-79°C, 125 mg, 50% yield, 88.1% ee. 1 H NMR (400MHz, CDCl3) δ: 7.42-7.25 (m, 7H), 7.19-7.08 (m, 2H), 6.47 (d, J = 15.8Hz, 1H), 6.24-6. 13(m,1H),3.92(q,J=7.1Hz,1H),2.97(dd,J=15.8,7.7Hz,1H),2.86(dd,J=15.8,7.7Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 167.8, 151.6, 136.3, 133.0, 129.0, 128.8, 128.2, 128.1, 127.9, 126.6, 125.0, 124.8, 117.3, 38.5, 35.5. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 6.16 min; t R (S) = 9.02 min. Characterization data of (R)-10a: white solid, mp 102-103 ° C, 124 mg, 49% yield, 88.7% ee. 1H NMR(400MHz, CDCl3)δ:7.40-7.27(m,4H),7.24-7.04(m,3H),6.96-6.82(m,2H),6.64(s,1H),6.57-6.44(m,2H),4.08(dt ,J=10.1,5.9Hz,1H),3.79(dt,J=10.1,4.8Hz,1H),3.52(td,J=10.1,4.0Hz,1H),2.26(m,1H),1.88(m,1H),1.68(s,1H). 13 C NMR (100MHz, CDCl3)154.1,137.5,132.8,129.9,129.6,128.7,128.6,127.8,127.4,126.3,121.4,116.7,60.7,37.4,37.0. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 29.29 min; t R (R)=34.57min.HRMS(ESI)Calcd for C 17 H 18 NaO2([M+Na] + ):277.1199,Found:277.1194.

[0094] Example 20:

[0095] The racemic substrate rac-9b (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9b (yield 49%, 89.0% ee) and (R)-10b (yield 48%, 89.6% ee). Characterization data of (S)-9b: white solid, mp 89-90°C, 129 mg, 49% yield, 89.0% ee.1 H NMR (400MHz, CDCl3) δ: 7.33-7.24 (m, 4H), 7.13-7.09 (m, 4H), 6.43 (d, J = 15.7Hz, 1H), 6.12 (dd, J = 15.7, 7. 6Hz, 1H), 3.89 (q, J = 7.2Hz, 1H), 2.96 (dd, J = 15.8, 5.7Hz, 1H), 2.84 (dd, J = 15.8, 7.7Hz, 1H), 2.33 (s, 3H). 13 C NMR(100MHz, CDCl3)δ:167.9,151.5,138.0,133.5,132.8,129.5,128.9,12 7.9,127.1,126.5,125.2,124.8,117.3,77.5,77.2,76.8,38.5,35.5,21.3. (c1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 15.90 min; t R (S) = 17.15 min. Characterization data of (R)-10b: white solid, mp 113-114 ° C, 128 mg, 48% yield, 89.6% ee. 1 H NMR (400MHz, CDCl3) δ: 7.26 (d, J = 7.9Hz, 2H), 7.18-7.16 (m, 1H), 7.13-7.06 (m ,3H),6.94-6.83(m,2H),6.50(d,J=16.1Hz,1H),6.41(dd,J=16.0,6.4Hz,1H) ,4.07(dt,J=10.0,5.9Hz,1H),3.77(dt,J=10.0,4.8Hz,1H),3.50(td,J=10.0 ,3.8Hz,1H),2.71(s,1H),2.32(s,3H),2.27-2.19(m,1H),1.89-1.81(m,1H). 13 CNMR(100MHz, CDCl3)δ:154.0,137.1,134.6,131.7,129.7,129.4,128.6,127.7,126.2,121.3,116.5,60.6,37.5,36.8,21.3. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 5.62 min; t R (R)=7.42min.HRMS(ESI)Calcd forC 18 H 21 O2([M+H] + ):269.1536,Found:269.1531.

[0096] Example 21:

[0097] The racemic substrate rac-9c (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times, then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9c (yield 48%, 90.3% ee) and (R)-10c (yield 47%, 94.3% ee). Characterization data of (S)-9c: colorless oil, 134 mg, 48% yield, 90.3% ee. 1 H NMR(400MHz, CDCl3)δ:7.33-7.27(m,3H),7.26-7.25(m,1H),7.14-7.09(m,2H),6.90-6.79(m,2H),6.40(d,J=15.8Hz,1H),6 .03(dd,J=15.8,7.6Hz,1H),3.88(q,J=7.5Hz,1H),3.81(s,3H),2.96(dd,J=15.8,5.7Hz,1H),2.84(dd,J=15.8,7.7Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 167.9, 159.6, 151.5, 132.3, 129.1, 128.9, 127.9, 127.8, 125.9, 125.3, 124.8, 117.3, 114.2, 55.4, 38.5, 35.6. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 8.97 min; t R (S) = 9.64 min. Characterization data of (R)-10c: colorless oil, 133 mg, 47% yield, 94.3% ee. 1 H NMR(400MHz, CDCl3)δ:7.35-7.23(m,3H),7.22-7.08(m,2H),6.96-6.81(m,4H),6.53-6.44(m,1H),6.36-6.3 0(m,1H),4.05-3.97(m,1H),3.80(s,4H),3.52(td,J=10.1,4.1Hz,1H),2.27-2.19(m,1H),1.92-1.84(m,2H). 13 C NMR(100MHz, CDCl3)δ:159.1,154.0,130.6,130.3,129.9,129.3,128.5,127.7,127.5,121.3,116.5,114.1,60.7,55.4,37.6,36.9., (c1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 19.12 min; t R (R)=20.71min.HRMS(ESI)Calcd for C 18 H 21 O3([M+H] + ):285.1485,Found:285.1482.

[0098] Example 22:

[0099] The racemic substrate rac-9d (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9d (yield 48%, 90.3% ee) and (R)-10d (yield 46%, 94.0% ee). Characterization data of (S)-9d: white solid, mp 104-105°C, 158 mg, 48% yield, 90.3% ee. 1 H NMR (400MHz, CDCl3) δ: 7.61 (d, J = 2.5Hz, 1H), 7.45-7.41 (m, 2H), 7.38 (s, 1H), 7.33-7.28 (m, 3 H),7.26-7.22(m,1H),6.78(d,J=8.6Hz,1H),4.54(dd,J=8.1,6.2Hz,1H),2.95-2.81(m,2H). 13 C NMR (100MHz, CDCl3) δ: 172.6, 152.8, 131.8, 131.5, 129.6, 128.4, 128.4, 122.9, 119.4, 113.1, 89.0, 83.9, 82.6, 43.0, 29.0, 28.1. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 22.94 min; t R (R) = 25.35 min. Characterization data of (R)-10d: white solid, mp 109-110 ° C, 153 mg, 46% yield, 94.0% ee. 1H NMR(400MHz, Methanol-d4)δ:7.39-7.32(m,2H),7.31-7.20(m,3H),7.20-7.08(m,2H),6.70(d,J=8 .5Hz,1H),6.51-6.36(m,2H),3.96-3.91(m,1H),3.55(t,J=6.8Hz,2H),2.02(qd,J=6.8,2.8Hz,2H). 13 C NMR(100MHz,MeOD)δ:154.0,137.6,132.9,132.1,130.6,129.8,129.4,128.1,126.7,125.7,116.7,111.0,59.7,38.9,37.1. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 10.60 min; t R (R)=11.40min.HRMS(ESI)Calcd for C 17 H 18 BrO2([M+H] + ):333.0485,Found:333.0481.

[0100] Example 23:

[0101] The racemic substrate rac-9e (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9e (yield 49%, 89.5% ee) and (R)-10e (yield 47%, 90.5% ee). Characterization data of (S)-9e: white solid, mp 106-107°C, 137 mg, 49% yield, 89.5% ee. H NMR (400 MHz, CDCl3) δ: 7.40 (dd, J = 7.6, 1.7 Hz, 1H), 7.30-7.20 (m, 3H), 7.17-7.06 (m, 2H), 6.93-6.81 (m, 3H), 6.18 (dd, J = 15.9, 8.0 Hz, 1H), 3.93-3.88 (m, 1H), 3.82 (s, 3H), 2.95 (dd, J = 15.9, 5.6 Hz, 1H), 2.81 (dd, J = 15.9, 8.6 Hz, 1H). 13 C NMR(100MHz, CDCl3)δ:167.9,156.8,151.5,129.1,128.8,128.6,128.0,1 27.9,127.1,125.4,125.3,124.7,120.7,117.1,111.0,55.5,39.0,35.6. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 15.63 min; t R (R) = 20.68 min. Characterization data of (R)-10e: white solid, mp 45-46 ° C, 133 mg, 47% yield, 90.5% ee 1HNMR(400MHz, CDCl3)δ:7.43(dd,J=7.7,1.7Hz,1H),7.24-7.17(m,2H),7.12-7.08(m,1H),6.93-6.84(m,5H),6.46(dd,J=16.2,7 .0Hz,1H),4.12-4.05(m,1H),3.83(s,3H),3.80-3.75(m,1H),3.51(td,J=10.3,3.9Hz,1H),2.30-2.22(m,1H),1.91-1.83(m,1H). 13 C NMR(100MHz, CDCl3)δ:156.6,154.1,133.3,129.9,128.6,128.4,127.7,126 .7,126.5,124.5,121.3,120.8,116.6,111.0,60.7,55.6,37.4,37.4,29.8., (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 9.53 min; t R (S)=10.19min.HRMS(ESI)Calcd forC 18 H 21 O3([M+H] + ):285.1485,Found:285.1481.

[0102] Example 24:

[0103] The racemic substrate rac-9f (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9f (yield 48%, 92.9% ee) and (R)-10f (yield 50%, 88.7% ee). Characterization data of (S)-9f: white solid, mp 121-122°C, 134 mg, 48% yield, 92.9% ee. 1 H NMR(400MHz, CDCl3)δ:7.41-7.28(m,4H),7.27-7.22(m,1H),7.13(d,J=8.4Hz,1H),6.77-6.60(m,2H),6.44(d,J=15.7Hz,1H ),6.15(dd,J=15.8,7.5Hz,1H),3.92-3.83(m,1H),3.81(s,3H),2.95(dd,J=15.8,5.7Hz,1H),2.82(dd,J=15.8,7.7Hz,1H). 13 CNMR(100MHz, CDCl3)δ:167.8,160.2,152.3,136.4,132.7,128.8,128.7,128.5,128.1,126.6,116.8,110.8,102.8,55.7,37.9,35.7. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 12.00 min; t R (S) = 13.52 min. Characterization data of (R)-10f: white solid, mp 120-121 ° C, 142 mg, 50% yield, 88.7% ee. 1HNMR(400MHz, CDCl3)δ:7.42-7.35(m,2H),7.30(dd,J=8.4,6.8Hz,2H),7.24-7.17(m,1H),7.05(d,J=8.3Hz,1H),6.62-6.37(m,4H),3.9 7(dt,J=10.6,5.6Hz,1H),3.85-3.80(m,1H),3.77(s,3H),3.52(td,J=10.3,3.8Hz,1H),2.24(td,J=9.7,5.0Hz,1H),1.88-1.81(m,1H). 13 C NMR (100MHz, CDCl3) δ: 159.1, 154.9, 137.5, 133.1, 129.4, 129.1, 128.6, 127.2, 126.3, 122.0, 106.6, 102.4, 102.3, 60.5, 55.4, 37.5, 36.1. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 13.40 min; t R (S)=20.53min.HRMS(ESI)Calcd forC 18 H 21 O3([M+H] + ):285.1485,Found:285.1482.

[0104] Example 25:

[0105] The racemic substrate rac-9g (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times, then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford the products (S)-9g (yield 50%, 90.0% ee) and (R)-10g (yield 49%, 96.2% ee). Characterization data of (S)-9f: white solid, mp 115-116°C, 132 mg, 50% yield, 90.0% ee. 1 H NMR(400MHz, CDCl3)δ:7.37-7.28(m,4H),7.26-7.22(m,1H),7.16-7.14(m,1H),7.10-7.01(m,2H),6.45 (d,J=15.8Hz,1H),6.18(dd,J=15.8,7.5Hz,1H),3.88(q,J=6.9Hz,1H),2.97–2.81(m,2H),2.33(s,3H). 13 C NMR (100MHz, CDCl3) δ: 168.0, 149.8, 132.6, 130.5, 128.7, 128.4, 128.0, 126.6, 126.6, 125.4, 124.8, 124.3, 38.6, 35.4, 15.9. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 8.99 min; t R (S) = 9.68 min. Characterization data of (R)-10f: white solid, mp 103-104 ° C, 131 mg, 49% yield, 96.2% ee. 1H NMR(400MHz, CDCl3)δ:7.33-7.23(m,2H),7.20-7.17(m,1H),7.06-6.89(m,2H),6.80(t,J=6.9Hz,1H),6.72(s,1H),6.52-6.38(m,2H),4.0 7-4.00(m,1H),3.72(dt,J=10.1,4.7Hz,1H),3.46(td,J=10.1,4.0Hz,1H),2.85(s,1H),2.25(s,3H),2.21-2.12(m,4H),1.88-1.80(m,1H). 13 C NMR (100MHz, CDCl3) δ: 152.3, 137.4, 132.9, 129.7, 129.3, 129.1, 128.6, 127.3, 126.3, 126.0, 125.3, 120.8, 60.5, 37.2, 37.1, 16.5. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 16.06 min; t R (R)=17.56min.HRMS(ESI)Calcd for C 18 H 21 O2([M+H] + ):269.1536,Found:269.1532.

[0106] Example 26:

[0107] The racemic substrate rac-9h (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9h (50% yield, 90.7% ee) and (R)-10h (48% yield, 91.2% ee). Characterization data of (S)-9h: white solid, mp 117-118 °C, 132 mg. 50% yield, 90.7% ee. 423 mg, 80% yield. 1 HNMR(400MHz, CDCl3)δ:7.39-7.29(m,4H),7.11-6.97(m,3H),6.47(d,J=15.8Hz,1H),6.17(dd,J=15.8,7 .6Hz, 1H), 3.86 (q, J=7.2Hz, 1H), 2.94 (dd, J=15.8, 5.7Hz, 1H), 2.83 (dd, J=15.8, 7.6Hz, 1H), 2.32 (s, 3H). 13 C NMR (100MHz, CDCl3) δ: 168.0, 149.5, 136.4, 134.5, 132.8, 129.5, 128.8, 128.3, 128.3, 128.1, 126.6, 124.7, 117.0, 38.6, 35.6, 20.9. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 7.01 min; t R (R) = 9.90 min. Characterization data of (R)-10h: white solid, mp 105-106 ° C, 129 mg, 48% yield, 91.2% ee. 1HNMR(400MHz, CDCl3)δ:7.42-7.35(m,2H),7.31(t,J=7.6Hz,2H),7.26-7.17(m,2H),6.98-6.88(m,2H),6.77(d,J=8.1Hz,1H),6.59-6.42(m,2H ),6.29(s,1H),4.04(dt,J=10.4,5.7Hz,1H),3.79(dt,J=10.4,4.8Hz,1 H),3.51(td,J=10.4,3.9Hz,1H),2.30-2.20(m,4H),1.89-1.82(m,1H). 13 C NMR (100MHz, CDCl3))δ:151.5,137.6,133.0,130.4,129.6,129.5,128.9,128.6,128.1,127.2,126.3,116.1,60.5,37.6,36.7,20.8. (c1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 9.92 min; t R (S)=15.49min.HRMS(ESI)Calcd for C 18 H 21 O2([M+H] + ):269.1536,Found:269.1530.

[0108] Example 27:

[0109] The racemic substrate rac-9i (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9i (yield 51%, 89.1% ee) and (R)-10i (yield 47%, 96.1% ee). Characterization data of (S)-9i: white solid, mp 97-98°C, 143 mg, 51% yield, 89.1% ee. 1 H NMR(400MHz, CDCl3)δ:7.38-7.26(m,5H),7.04(d,J=8.8Hz,1H),6.83(dd,J=8.8,3.0Hz,1H),6.77(dd,J=2.9,0.8Hz,1H),6.48(d,J=15 .8Hz,1H),6.17(dd,J=15.8,7.6Hz,1H),3.87(q,J=7.2Hz,1H),3.79(s,3H),2.94(dd,J=15.8,5.7Hz,1H),2.82(dd,J=15.9,7.7Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 168.0, 156.5, 145.5, 136.3, 133.0, 128.8, 128.1, 128.0, 126.6, 126.1, 118.1, 113.8, 113.1, 55.9, 38.8, 35.4. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 5.54 min; t R (S) = 5.80 min. Characterization data of (R)-10i: white solid, mp 97-98 ° C, 133 mg, 47% yield, 96.1% ee. 1H NMR(400MHz, CDCl3)δ:7.35(d,J=7.1Hz,2H),7.31-7.24(m,2H),7.24-7.13(m,1H),6 .81(d,J=8.7Hz,1H),6.73(d,J=3.0Hz,1H),6.65(dd,J=8.7,3.1Hz,1H),6.52(d,J=16 .0Hz,1H),6.43(dd,J=16.0,6.3Hz,1H),4.08(dt,J=10.9,6.0Hz,1H),3.80-3.74(m, 1H),3.72(s,3H),3.48(td,J=10.4,3.8Hz,1H),2.26-2.18(m,1H),1.87-1.79(m,1H). 13 C NMR (100MHz, CDCl3) δ: 154.1, 147.9, 137.4, 132.6, 131.0, 130.0, 128.6, 127.4, 126.3, 117.3, 114.4, 112.3, 60.6, 55.8, 37.5, 37.0. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 16.56 min; t R (R)=18.86min.HRMS(ESI)Calcd forC 18 H 21 O3([M+H] + ):285.1485,Found:285.1483.

[0110] Example 28:

[0111] The racemic substrate rac-9j (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9j (yield 49%, 93.3% ee) and (R)-10j (yield 47%, 93.8% ee). Characterization data of (S)-9j: white solid, mp 101-102°C, 125 mg, 49% yield, 93.3% ee. 1 H NMR(400MHz, CDCl3)δ:7.34-7.29(m,1H),7.24-7.23(m,1H),7.17-7.09(m,3H),7.04-6.91(m,2H),6.54(d,J=15.7Hz ,1H),6.02(dd,J=15.6,7.4Hz,1H),3.87(q,J=6.9Hz,1H),2.95(dd,J=15.8,5.8Hz,1H),2.84(dd,J=15.9,7.4Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 167.6, 151.5, 141.2, 129.0, 127.9, 127.7, 127.5, 126.3, 126.0, 124.8, 124.8, 124.7, 117.3, 38.3, 35.3. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 13.72 min; t R (R) = 18.30 min. Characterization data of (R)-10j: white solid, mp 108-109 ° C, 122 mg, 47% yield, 93.8% ee. 1HNMR(400MHz, CDCl3)δ:7.20-7.09(m,3H),6.97-6.84(m,4H),6.70-6.61(m,1H),6.31(dd,J=15.8,6.8Hz,2H),4.15–3.9 7(m,0H),3.79(dt,J=10.2,4.8Hz,1H),3.51(td,J=10.2,4.0Hz,1H),2.27-2.18(m,1H),1.96(s,1H),1.89-1.82(m,1H). 13 C NMR (100MHz, CDCl3) δ: 154.0, 142.7, 132.6, 129.4, 128.6, 127.8, 127.4, 125.2, 123.8, 123.3, 121.4, 116.6, 60.6, 37.4, 36.8. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 8.93 min; t R (R)=9.60min.HRMS(ESI)Calcd for C 15 H 17 SO2([M+H] + ):261.0944,Found:261.0940.

[0112] Example 29:

[0113] The racemic substrate rac-9k (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9k (yield 49%, 88.1% ee) and (R)-10k (yield 47%, 92.0% ee). Characterization data of (S)-9k: Colorless oil, 85 mg, 49% yield, 88.1% ee. 1H NMR (400MHz, CDCl3) δ: 7.24 (dd, J=27.7, 8.5Hz, 2H), 7.11 (ddd, J=29.2, 8.1, 3.3Hz, 2H), 5.86 (qd, J=10.2, 4.3Hz, 1 H),5.24(dd,J=10.4,3.3Hz,1H),5.11(dd,J=17.1,3.4Hz,1H),3.81-3.67(m,1H),2.93-2.85(m,1H),2.78(m,1H). 13 C NMR (100MHz, CDCl3) δ: 167.8, 151.6, 136.9, 128.9, 127.8, 124.7, 117.9, 117.2, 39.0, 35.0. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 12.18 min; t R (S) = 18.11 min. Characterization data of (R)-10k: white solid, mp 43-44 ° C, 84 mg, 47% yield, 92.0% ee. 1 H NMR(400MHz, CDCl3)δ:7.14-7.10(m,2H),7.01-6.79(m,2H),6.14-6.06(m,1H),5.28-5.10(m,2H),3.90(dt,J=11 .6,6.0Hz,1H),3.77(dt,J=10.3,4.7Hz,1H),3.47(td,J=10.4,3.8Hz,1H),2.21-2.13(m,1H),1.80-1.72(m,1H). 13 C NMR (100MHz, CDCl3) δ: 154.1, 141.0, 129.3, 128.5, 127.7, 121.2, 116.6, 114.7, 60.6, 37.4, 36.7. (c1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 8.07 min; t R (S)=12.54min.HRMS(ESI)Calcd for C 11 H15 O2([M+H] + ):179.1067,Found:179.1063.

[0114] Example 30:

[0115] The racemic substrate rac-9l (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-9l (yield 48%, 93.7% ee) and (R)-10l (yield 50%, 90.3% ee). Characterization data of (S)-9l: colorless oil, 97 mg, 48% yield, 93.7% ee. 1 H NMR(400MHz, CDCl3)δ:7.28-7.24(m,2H),7.17-7.15(m,1H),7.14-7.04(m,2H),5.10(d,J=9.3Hz,1H),3.95(t d,J=10.0,5.2Hz,1H),2.82(dd,J=15.8,5.2Hz,1H),2.56(dd,J=15.8,10.6Hz,1H),1.81(s,3H),1.75(s,3H). 13 C NMR (100MHz, CDCl3) δ: 168.5, 151.7, 136.2, 128.5, 127.3, 126.4, 124.6, 123.1, 117.1, 35.8, 33.7, 25.9, 18.3. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 21.48 min; t R (R) = 23.62 min. Characterization data of (R)-101: white solid, mp 54-55 ° C, 103 mg, 50% yield, 90.3% ee. 1H NMR(400MHz, CDCl3)δ:7.15(d,J=7.5Hz,1H),7.05(t,J=7.5Hz,1H),6.89(t,J=7.5Hz,1H),6.81(d,J=8.0Hz,1H),5.45(d,J=8.9Hz,1H),4 .06(q,J=8.3Hz,1H),3.73-3.63(m,1H),3.46(td,J=9.8,9.4,3.7Hz,1H),2.03-1.94(m,1H),1.77-1.75(m,1H),1.72(s,3H),1.61(s,3H). 13 C NMR(100MHz, CDCl3)δ:153.6,133.4,131.3,128.0,127.4,127.1,121.2,116.1,60.8,39.4,32.5,25.9,18.3., (c1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 9.14 min; t R (R) = 9.84 min.

[0116] Example 31:

[0117] Alkynyl or substituted alkynyl substrate structures (substrates 11a to 11o) and reaction equations:

[0118]

[0119] The racemic substrate rac-11a (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times, then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11a (50% yield, 88.2% ee) and (R)-12a (48% yield, 88.9% ee). Characterization data of (S)-11a: colorless oil, 93 mg, 50% yield, 88.2% ee. 1 H NMR(400MHz, CDCl3)δ:7.49(dt,J=7.6,1.2Hz,1H),7.30(td,J=7.7,1.6Hz,1H),7.17(td,J=7.6,1.2Hz,1H),7.05(dd,J =8.1,1.2Hz,1H),4.03-3.98(m,1H),2.98(dd,J=15.8,5.2Hz,1H),2.82(dd,J=15.8,10.0Hz,1H),1.86(d,J=2.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ: 167.3, 150.9, 129.1, 127.4, 124.8, 123.5, 117.1, 81.4, 75.9, 36.0, 27.6, 3.7. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 14.45 min; t R (R) = 16.94 min. Characterization data of (R)-12a: colorless oil, 91 mg, 48% yield, 88.9% ee. 1H NMR(400MHz, CDCl3)δ:7.42-7.34(m,1H),7.16-7.10(m,1H),6.92(td,J=7.5,2.7Hz,1H),6.83(dd,J=8.1, 2.7Hz,1H),4.12-4.06(m,1H),3.86-3.75(m,1H),3.63-3.56(m,1H),2.14-2.05(m,1H),1.94-1.85(m,4H). 13 C NMR (100MHz, CDCl3) δ: 153.7, 129.1, 128.3, 127.5, 121.1, 116.7, 80.2, 79.4, 60.6, 39.4, 28.9, 3.7. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 13.35 min; t R (S)=14.20min.HRMS(ESI)Calcd for C 12 H 15 O2([M+H] + ):191.2495,Found:191.2491.

[0120] Example 32:

[0121] The racemic substrate rac-11b (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11b (yield 49%, 88.5% ee) and (R)-12b (yield 46%, 93.3% ee). Characterization data of (S)-11b: Colorless oil, 106 mg, 49% yield, 88.5% ee. 1H NMR(400MHz, CDCl3)δ:7.49-7.46(m,1H),7.33-7.28(m,1H),7.17(td,J=7.5,1.3Hz,1H),7.06(dd,J=8.1,1.3Hz,1H),4.01(dd,J=10 .4,5.2Hz,1H),2.99(dd,J=15.8,5.2Hz,1H),2.80(dd,J=15.8,10.4Hz,1H),1.30-1.24(m,1H),0.82-0.74(m,2H),0.71-0.64(m,2H). 13 C NMR (100MHz, CDCl3) δ: 167.2, 151.0, 129.2, 127.5, 124.9, 123.6, 117.1, 89.1, 72.0, 36.1, 27.7, 8.5, 8.4, -0.4. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 4.38 min; t R (S) = 5.20 min. Characterization data of (R)-12b: white solid, mp 78-79 ° C, 99 mg, 46% yield, 93.3% ee, 1 H NMR (400MHz, CDCl3) δ: 7.34 (dd, J=7.6, 1.8Hz, 1H), 7.13 (td, J=7.6, 1.8Hz, 1H), 6.94-6.89 (m, 1H), 6.82 (dd, J=8.1, 1.2Hz, 1H), 4.06 (td, J=7. 6,1.8Hz,1H),3.81-3.75(m,1H),3.61-3.56(m,1H),2.43(s,1H),2.12 -2.03(m,1H),1.92-1.84(m,1H),1.34-1.24(m,1H),0.88-0.55(m,4H). 13 C NMR (100MHz, CDCl3) δ: 153.7, 129.0, 128.3, 127.5, 121.1, 116.6, 87.2, 76.3, 60.6, 39.5, 28.8, 8.4, 8.3, -0.3. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 16.73 min; t R (S)=23.96min.HRMS(ESI)Calcd forC 14 H 17 O2([M+H] + ):217.2875,Found:217.2872.

[0122] Example 33:

[0123] The racemic substrate rac-11c (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11c (yield 52%, 85.7% ee) and (R)-12c (yield 44%, 95.5% ee). Characterization data of (S)-11c: Colorless oil, 125 mg, 52% yield, 85.7% ee. 1 H NMR (400MHz, CDCl3) δ: 7.50 (d, J = 7.7Hz, 1H), 7.32-7.30 (m, 1H), 7.17 (t, J = 7.7Hz, 1H), 7.06 (d, J = 8.1Hz, 1H), 4.10-3.97 (m, 1H), 3. 04-2.98(m,,1H),2.84-2.76(m,1H),2.71-2.59(m,1H),1.96-1.92(m,2H),1.76-1.70(m,2H),1.65-1.44(m,6H),1.34-1.23(m,1H). 13C NMR (100MHz, CDCl3) δ: 167.3, 151.1, 129.1, 127.5, 124.9, 123.8, 117.1, 90.5, 76.2, 36.2, 34.1, 30.3, 27.7, 25.1. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 10.84 min; t R (R) = 11.64 min. Characterization data of (R)-12c: colorless oil, 122 mg, 44% yield, 95.5% ee. 1 H NMR(400MHz, CDCl3)δ:7.22(d,J=7.6Hz,1H),7.07(t,J=7.6Hz,1H),6.83(t, J=7.6Hz,1H),6.77(d,J=8.1Hz,1H),6.53(s,1H),3.96(t,J=7.5Hz,1H),3.74 (dt,J=11.2,5.6Hz,1H),3.59-3.53(m,1H),2.63-2.55(m,1H),2.04-1.97(m ,1H),1.86(td,J=9.7,7.5,4.4Hz,3H),1.69-1.62(m,2H),1.60-1.45(m,5H). 13 C NMR (100MHz, CDCl3) δ: 154.0, 129.1, 128.3, 127.4, 121.1, 117.0, 89.3, 80.3, 60.7, 39.5, 34.1, 30.4, 29.6, 25.1. (c1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 8.32 min; t R (S)=9.29min.HRMS(ESI)Calcd for C 16 H 21 O2([M+H] + ):245.3415,Found:234.3411.

[0124] Example 34:

[0125] The racemic substrate rac-11d (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11d (yield 49%, 91.4% ee) and (R)-12d (yield 48%, 93.4% ee). Characterization data of (S)-11d: White oil, mp 116-117°C, 122 mg, 49% yield, 91.4% ee. 1 H NMR(400MHz, CDCl3)δ:7.59(dt,J=7.8,1.3Hz,1H),7.49-7.42(m,2H),7.36-7.30(tt,J=4.6,2.4Hz,4H),7.21(td,J=7.6,1.3H z,1H),7.11(dd,J=8.1,1.3Hz,1H),4.31(dd,J=10.6,5.1Hz,1H),3.14(dd,J=15.9,5.1Hz,1H),2.96(dd,J=15.9,10.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 166.9, 151.1, 131.9, 129.4, 128.7, 128.5, 127.6, 125.0, 122.9, 122.5, 117.3, 85.9, 85.6, 35.8, 28.3. (c 1.0,MeOH)[lit. 15 (c 0.85, CHCl3, 72% ee)]. HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 8.95 min; t R (S) = 9.62 min. Characterization data of (R)-12d: white solid, mp 105-106 ° C, 121 mg, 48% yield, 93.4% ee. 1H NMR(400MHz, CDCl3)δ:7.53-7.40(m,3H),7.32-7.30(m,3H),7.20-7.15(dt,J=7.5,1.7Hz,1H),6.96(td,J=7.5,1.2Hz,1H),6.87(dd,J=8 .0,1.2Hz,1H),6.24(s,1H),4.37(t,J=7.5Hz,1H),3.89(dt,J=10.8,5.4Hz,1H),3.69-3.63(m,1H),2.31-2.22(m,1H),2.06-1.98(m,1H). 13 C NMR (100MHz, CDCl3) δ: 153.5, 131.8, 129.2, 128.5, 128.4, 128.2, 127.1, 123.3, 121.4, 116.6, 90.9, 83.5, 60.6, 39.5, 28.9. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 6.65 min; t R (S) = 7.12 min.

[0126] Example 35:

[0127] The racemic substrate rac-11e (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11e (yield 48%, 95.5% ee) and (R)-12e (yield 50%, 93.4% ee). Characterization data of (S)-11e: white solid, mp 112-113°C, 126 mg, 48% yield, 95.5% ee. 1H NMR(400MHz, CDCl3)δ:7.60-7.57(m,J=7.5,1.3Hz,1H),7.3-7.30(m,3H),7.20(td,J=7.5,1.3Hz,1H),7.16-7.0 7(m,3H),4.29(dd,J=10.6,5.1Hz,1H),3.13(dd,J=15.9,5.1Hz,1H),2.94(dd,J=15.9,10.6Hz,1H),2.35(s,3H). 13 C NMR (100MHz, CDCl3) δ: 166.9, 151.2, 138.9, 131.8, 129.4, 129.2, 127.6, 125.0, 123.1, 119.4, 117.3, 85.7, 85.2, 35.8, 28.3, 21.6. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 15.05 min; t R (S) = 16.22 min. Characterization data of (R)-12e: white solid, mp 116-117 ° C, 133 mg, 50% yield, 93.4% ee. 1 HNMR(400MHz, CDCl3)δ:7.47(dd,J=7.7,1.7Hz,1H),7.40-7.28(m,2H),7.17(td,J=7.7,1.7Hz,1H),7.11(d,J=7.9Hz,2H),6.95(td,J=7.5,1.2Hz ,1H),6.87(dd,J=8.0,1.2Hz,1H),4.34(t,J=7.5Hz,1H),3.92-3.83(m,1 H),3.69-3.63(m,1H),2.34(s,3H),2.29-2.21(m,1H),2.05-1.98(m,1H). 13 C NMR (100MHz, CDCl3) δ: 153.5, 138.2, 131.7, 129.1, 128.4, 127.3, 121.3, 120.2, 116.4, 90.1, 83.5, 60.6, 39.5, 28.8, 21.6. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 10.66 min; t R (S) = 11.07 min.

[0128] Example 36:

[0129] The racemic substrate rac-11f (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11f (yield 51%, 90.4% ee) and (R)-12f (yield 48%, 91.8% ee). Characterization data of (S)-11f: white solid, mp 117-118°C, 142 mg, 51% yield, 90.4% ee. 1 H NMR (400MHz, CDCl3) δ: 7.59 (dt, J=7.8, 1.4Hz, 1H), 7.44-7.36 (m, 2H), 7.35-7.30 (m, 1H), 7.20 (td, J=7.5, 1.2Hz, 1H), 7.10 (dd, J=8.0, 1.2Hz,1H),6.90-6.79(m,2H),4.29(dd,J=10.5,5.2Hz,1H),3.82(s,3H),3.12(dd,J=15.9,5.2Hz,1H),2.94(dd,J=15.9,10.5Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 167.0, 160.0, 151.2, 133.4, 129.4, 127.6, 125.0, 123.2, 117.3, 114.6, 114.1, 85.5, 84.5, 55.5, 35.9, 28.3. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 9.38 min; t R (S) = 10.56 min. Characterization data of (R)-12f: white solid, mp 117-118 ° C, 135 mg, 48% yield, 91.8% ee. 1 H NMR(400MHz, CDCl3)δ:7.45(dd,J=7.6,1.7Hz,1H),7.42-7.34(m,2H),7.20-7.14(m,1H),6.95(td,J=7.6,1.2Hz,1H),6.92-6.80(m ,3H),6.26(s,1H),4.32(t,J=7.5Hz,1H),3.89-3.85(m,1H),3.81(s,3H),3.69-3.63(m,1H),2.29-2.22(m,1H),2.04-1.99(m,1H). 13 CNMR(100MHz,MeOD)δ:160.8,155.2,133.9,133.9,129.5,128.7,120.7,117.3,116.0,114.9,90.6,83.5,61.3,55.7,40.6,29.5. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 15.98 min; t R (S) = 17.69 min.

[0130] Example 37:

[0131] The racemic substrate rac-11g (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford the products (S)-11g (yield 49%, 95.6% ee) and (R)-12g (yield 47%, 99.7% ee). Characterization data of (S)-11g: white solid, mp 135-136°C, 160 mg, 49% yield, 95.6% ee. 1 H NMR(400MHz, CDCl3)δ:7.56-7.54(m,1H),7.48-7.42(m,2H),7.37-7.29(m,3H),7.21(td,J=7.5,1.2Hz,1H),7.11 (dd,J=8.1,1.2Hz,1H),4.29(dd,J=10.1,5.2Hz,1H),3.12(dd,J=15.8,5.2Hz,1H),2.96(dd,J=15.8,10.1Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 166.6, 151.2, 133.4, 131.8, 129.5, 127.5, 125.1, 123.1, 122.6, 121.4, 117.4, 87.2, 84.6, 35.6, 28.3. (c 1.0, MeOH). HPLC conditions: Chiralcel AS-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 11.42 min; t R (S) = 13.32 min. Characterization data of (R)-12 g: white solid, mp 135136 ° C, 156 mg, 47% yield, 99.7% ee. 1H NMR (400MHz, CDCl3) δ: 7.49 (dd, J=7.6, 1.7Hz, 1H), 7.47-7.36 (m, 2H), 7.35-7.26 (m, 2H), 7.16 (td, J=7.6, 1.7Hz, 1H), 6.96 (td, J=7.6, 1. 2Hz,1H),6.85(dd,J=8.0,1.2Hz,1H),4.40(t,J=8.0Hz,1H),3.86-3.84(m,1H),3.66-3.60(m,1H),2.28-2.21(m,1H),2.04-1.97(m,1H). 13 C NMR(100MHz, CDCl3)δ:153.4,133.3,131.6,129.1,128.5,127.0,122.4,121.4,116.5,92.3,82.2,60.5,39.4,28.6., (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 9.94 min; t R (R)=15.58min.HRMS(ESI)Calcd forC 17 H 16 O2Br([M+H] + ):332.2165,Found:332.2161.

[0132] Example 38:

[0133] The racemic substrate rac-11h (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11h (yield 51%, 92.1% ee) and (R)-12h (yield 46%, 93.9% ee). Characterization data of (S)-11h: white solid, mp 106-107°C, 134 mg, 51% yield, 92.1% ee. 1 H NMR(400MHz, CDCl3)δ:7.50-7.42(m,2H),7.40-7.28(m,4H),7.15-7.10(m,1H),6.99(d,J=8.2Hz,1H), 4.27(dd,J=10.3,5.2Hz,1H), 3.11(dd,J=15.8,5.2Hz,1H), 2.94(dd,J=15.8,10.3Hz,1H), 2.37(s,3H). 13 C NMR (100MHz, CDCl3) δ: 167.1, 149.1, 134.7, 131.9, 129.9, 128.7, 128.5, 127.9, 122.6, 122.5, 117.1, 86.1, 85.4, 35.9, 28.2, 21.0. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 11.37 min; t R (S) = 18.80 min. Characterization data of (R)-12h: white solid, mp 108-109 ° C, 122 mg, 46% yield, 93.9% ee. 1H NMR (400MHz, CDCl3) δ: 7.45 (dd, J=6.6, 3.0Hz, 2H), 7.36-7.26 (m, 4H), 6.96 (dd, J=8.1, 2.1Hz, 1H), 6.76 (d, J=8.1Hz, 1H), 6.29 ( s,1H),4.34(t,J=7.5Hz,1H),3.87(dt,J=10.7,5.2Hz,1H),3.64(td,J=10.7,4.1Hz,1H),2.29-2.21(m,4H),2.03-1.96(m,1H). 13 C NMR (100MHz, CDCl3) δ: 164.9, 158.4, 151.3, 131.8, 130.6, 129.6, 129.0, 128.4, 128.2, 126.8, 123.4, 116.7, 90.9, 60.5, 50.1, 39.6, 29.0, 20.8. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 9.05 min; t R (S) = 9.64 min.

[0134] Example 39:

[0135] The racemic substrate rac-11i (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11i (yield 52%, 88.0% ee) and (R)-12i (yield 45%, 92.2% ee). Characterization data of (S)-11i: white solid, mp 114-115°C, 136 mg, 52% yield, 88.0% ee. 1H NMR(400MHz, CDCl3)δ:7.60(dt,J=7.6,1.4Hz,1H),7.44-7.30(m,2H),7.25-7.07(m,4H),4.35(d d,J=10.3,5.1Hz,1H),3.15(dd,J=15.8,5.1Hz,1H),2.98(dd,J=15.8,10.3Hz,1H),2.42(s,3H). 13 C NMR (100MHz, CDCl3) δ: 166.9, 151.1, 140.3, 132.1, 129.6, 129.3, 128.6, 127.5, 125.6, 125.0, 123.1, 122.2, 117.2, 89.8, 84.4, 35.9, 28.4, 20.8. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 9.58 min; t R (R) = 10.34 min. Characterization data of (R)-12i: white solid, mp 107-108 ° C, 120 mg, 45% yield, 92.2% ee. 1 H NMR(400MHz, CDCl3)δ:7.50(dd,J=7.7,1.7Hz,1H),7.44-7.37(m,1H),7.26-7.06(m,4H),6.96(td,J=7.5,1.2Hz,1H),6.87(dd,J=8.0,1.2Hz,1H),6 .29(s,1H),4.42(t,J=7.5Hz,1H),3.90(dt,J=10.8,5.3Hz,1H),3.70-3.6 5(m,1H),2.45(s,3H),2.33-2.24(m,1H),2.08-2.00(m,1H),1.90(s,1H). 13 CNMR(100MHz, CDCl3)δ:153.3,140.2,132.1,129.5,129.0,128.3,128.1,127.5,125.6,123.2,121.2,116.1,95.1,82.2,60.6,39.7,28.7,20.9. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 8.94 min; t R (R) = 9.94 min.

[0136] Example 40:

[0137] The racemic substrate rac-11j (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11j (yield 47%, 93.3% ee) and (R)-12j (yield 47%, 92.9% ee). Characterization data of (S)-11j: white solid, mp 114-115°C, 131 mg, 47% yield, 93.3% ee. 1 H NMR (400MHz, CDCl3) δ: 7.69 (dt, J=7.5, 1.3Hz, 1H), 7.41 (dd, J=7.5, 1.8Hz, 1H), 7.35-7.28 (m, 2H), 7.21 (td, J=7.5, 1.3Hz, 1H), 7.09 (dd, J= 8.1,1.2Hz,1H),6.94-6.86(m,2H),4.37(dd,J=11.3,5.0Hz,1H),3.89(s,3H),3.17(dd,J=15.9,5.0Hz,1H),2.96(dd,J=15.9,11.3Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 167.0, 160.4, 151.2, 133.7, 130.2, 129.3, 127.8, 125.0, 123.1, 120.6, 117.2, 111.7, 110.8, 82.0, 55.9, 35.8, 28.5. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 10.52 min; t R (R) = 11.94 min. Characterization data of (R)-12j: white solid, mp 109-110 ° C, 133 mg, 47% yield, 92.9% ee. 1 H NMR(400MHz, CDCl3)δ:7.41-7.37(m,2H),7.32-7.26(m,1H),7.17(td,J=7.7,1.7Hz,1H),6.98-6.83(m,4H),6.49 (s,1H),4.30(t,J=7.5Hz,1H),3.90(s,4H),3.76-3.71(m,1H),2.27-2.20(m,1H),2.13-2.05(m,1H),1.74(s,1H). 13 C NMR (100MHz, CDCl3) δ: 160.3, 154.0, 133.1, 129.8, 129.4, 128.5, 127.3, 121.2, 120.6, 117.4, 110.6, 94.7, 80.6, 77.4, 60.9, 55.9, 39.1, 31.0. (c 1.0, MeOH). HPLC conditions: Chiralcel AS-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 39.16 min; t R (S) = 48.12 min.

[0138] Example 41:

[0139] The racemic substrate rac-11k (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times, then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11k (yield 51%, 90.2% ee) and (R)-12k (yield 47%, 92.3% ee). Characterization data of (S)-11k: white solid, mp 118-119°C, 134 mg, 51% yield, 90.2% ee. 1 H NMR(400MHz, CDCl3)δ:7.53-7.42(m,2H),7.40-7.27(m,4H),7.12(dd,J=8.3,2.1Hz,1H),6.99(d,J=8.3Hz, 1H), 4.26 (dd, J=10.3, 5.2Hz, 1H), 3.11 (dd, J=15.9, 5.2Hz, 1H), 2.94 (dd, J=15.9, 10.3Hz, 1H), 2.37 (s, 3H). 13 C NMR (100MHz, CDCl3) δ: 167.1, 149.1, 134.7, 131.9, 129.9, 128.7, 128.5, 127.9, 122.6, 122.5, 117.1, 86.1, 85.5, 35.9, 28.2, 21.0. (c1.0, MeOH). HPLC conditions: Chiralcel AS-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 9.11 min; t R (S) = 9.81 min. Characterization data of (R)-12k: white solid, mp 105-106 ° C, 125 mg, 47% yield, 92.3% ee. 1HNMR(400MHz,MeOD)δ:7.48-7.38(m,2H),7.35-7.28(m,J=6.9,6.1,2.3Hz,4H),6.87(dd,J=8.2,2.2Hz,1H),6.67( d,J=8.1Hz,1H),4.36(dd,J=9.0,5.6Hz,1H),3.82-3.67(m,2H),2.25(s,3H),2.10-2.02(m,1H),1.96-1.87(m,1H). 13 C NMR (100MHz, MeOD) δ: 152.9, 132.5, 129.9, 129.8, 129.4, 129.1, 128.9, 128.8, 125.3, 115.9, 92.5, 83.6, 61.3, 40.6, 29.4, 20.8. (c 1.0, MeOH). HPLC conditions: Chiralcel AS-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 16.15 min; t R (R) = 17.54 min.

[0140] Example 42:

[0141] The racemic substrate rac-11l (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11l (50% yield, 85.6% ee) and (R)-12l (47% yield, 96.8% ee). Characterization data of (S)-111: white solid, mp 121-122°C, 139 mg, 50% yield, 85.6% ee. 1H NMR(400MHz, CDCl3)δ:7.48-7.40(m,2H),7.30-7.19(m,3H),7.10(d,J=3.0Hz,1H),7.00(d,J=8.9Hz,1H),6.82(dd,J=8 .9,3.0Hz,1H),4.24(dd,J=10.5,5.2Hz,1H),3.80(s,3H),3.08(dd,J=15.9,5.2Hz,1H),2.90(dd,J=15.9,10.5Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 166.9, 156.5, 144.9, 131.8, 128.6, 128.4, 123.8, 122.3, 117.9, 114.2, 112.6, 85.8, 85.5, 55.7, 35.5, 28.3. (c 1.0, MeOH). HPLC conditions: Chiralcel AS-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 5.38 min; t R (S) = 5.65 min. Characterization data of (R)-12l: white solid, mp 96-97 ° C, 133 mg, 47% yield, 96.8% ee. 1 HNMR (400MHz, CDCl3) δ: 7.53-7.36 (m, 2H), 7.34-7.26 (m, 3H), 7.08 (d, J = 3.1Hz, 1H), 6.81 (d, J = 8.7Hz, 1H), 6.72 (dd, J = 8. 7,3.1Hz,1H),4.41-4.31(m,1H),3.90-3.84(m,1H),3.78(s,3H),3.65-3.59(m,1H),2.32-2.23(m,1H),2.05-1.96(m,1H). 13 CNMR(100MHz, CDCl3)δ:154.2,147.5,131.8,128.4,128.2,123.3,117.6,114.5,113.5,90.7,83.5,77.2,76.8,60.5,55.9,39.5,29.2. (c 1.0, MeOH). HPLC conditions: Chiralcel AS-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 8.96 min; t R (S) = 9.57 min.

[0142] Example 43:

[0143] The racemic substrate rac-11m (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11m (yield 51%, 93.7% ee) and (R)-12m (yield 48%, 92.7% ee). Characterization data of (S)-11m: white solid, mp 135-136°C, 167 mg, 51% yield, 93.7% ee. 1 H NMR(400MHz, CDCl3)δ:7.71(d,J=2.3Hz,1H),7.48-7.44(m,3H),7.39-7.29(m,3H),6.99(d,J=8.6 Hz,1H),4.29(dd,J=10.6,5.2Hz,1H),3.13(dd,J=15.9,5.2Hz,1H),2.94(dd,J=15.9,10.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 166.0, 150.2, 132.4, 131.9, 130.4, 128.9, 128.5, 125.0, 122.1, 119.0, 117.6, 86.1, 85.0, 35.3, 28.1. (c 1.0, MeOH). HPLC conditions: Chiralcel AS-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 11.18 min; t R (R) = 12.07 min. Characterization data of (R)-12m: white solid, mp 129-130 ° C, 159 mg, 48% yield, 92.7% ee. 1 H NMR (400MHz, CDCl3) δ: 7.60 (d, J = 2.5Hz, 1H), 7.49-7.44 (m, 2H), 7.37-7.27 (m, 4H), 6.77 (d, J = 8.6Hz, 1 H), 4.33 (t, J = 7.5Hz, 1H), 3.93-3.88 (m, 1H), 3.67-3.60 (m, 1H), 2.31-2.23 (m, 1H), 2.06-1.97 (m, 1H). 13 C NMR (100MHz, CDCl3) δ: 152.7, 131.9, 131.2, 129.6, 128.5, 128.4, 123.1, 121.4, 118.4, 113.3, 90.0, 83.9, 60.5, 39.3, 28.6. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 11.52 min; t R (R)=16.72min.HRMS(ESI)Calcd for C 17 H 16 O2Br([M+H] + ):332.2165,Found:332.2161.

[0144] Example 44:

[0145] The racemic substrate rac-11n (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11n (yield 51%, 81.7% ee) and (R)-12n (yield 43%, 86.3% ee). Characterization data of (S)-11n: white solid, mp 109-110°C, 142 mg, 51% yield, 81.7% ee. 1 H NMR(400MHz, CDCl3)δ:7.50-7.41(m,3H),7.37-7.28(m,3H),6.75(dd,J=8.4,2.5Hz,1H),6.65(d,J=2.5Hz, 1H), 4.25 (dd, J=10.3, 5.1Hz, 1H), 3.82 (s, 3H), 3.11 (dd, J=15.8, 5.0Hz, 1H), 2.94 (dd, J=15.8, 5.0Hz, 1H). 13 C NMR (100MHz, CDCl3) δ: 166.9, 160.5, 151.9, 131.9, 128.6, 128.5, 128.1, 122.5, 114.7, 110.9, 102.9, 86.4, 85.2, 55.7, 36.0, 29.8, 27.6. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 11.52 min; t R (S) = 13.30 min. Characterization data of (R)-12n: white solid, 99-100 ° C, 121 mg, 43% yield, 86.3% ee. 1H NMR (400MHz, CDCl3) δ: 7.44 (dd, J=6.6, 3.1Hz, 2H), 7.37 (d, J=8.5Hz, 1H), 7.33-7.27 (m, 3H), 6.76 (s, 1H), 6.53 (dd, J=8.5, 2.6Hz, 1H), 6.45 (d, J=2 .6Hz,1H),4.30(t,J=7.5Hz,1H),3.88(dt,J=10.6,5.2Hz,1H),3.78(s,3 H),3.66-3.61(m,1H),2.30-2.21(m,1H),2.15(s,1H),2.01-1.92(m,1H). 13 C NMR (100MHz, CDCl3) δ: 159.9, 154.6, 131.8, 131.8, 129.7, 128.4, 128.2, 123.3, 119.3, 107.0, 102.6, 91.1, 83.4, 60.5, 55.5, 39.6, 28.4. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 12.83 min; t R (S) = 13.82 min.

[0146] Example 45:

[0147] The racemic substrate rac-11o (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-11o (50% yield, 93.2% ee) and (R)-12o (48% yield, 92.6% ee). Characterization data of (S)-11o: white solid, mp 123-124°C, 127 mg, 50% yield, 93.2% ee. 1H NMR(400MHz, CDCl3)δ:7.57-7.55(m,1H),7.38-7.32(m,1H),7.29-7.26(m,1H),7.24-7.18(m,2H),7.11(dd,J=8.1,1.3Hz, 1H), 6.98 (dd, J=5.2, 3.6Hz, 1H), 4.34 (dd, J=10.5, 5.2Hz, 1H), 3.14 (dd, J=15.9, 5.2Hz, 1H), 2.96 (dd, J=15.9, 10.5Hz, 1H). 13 C NMR (100MHz, CDCl3) δ: 166.6, 151.1, 132.6, 129.5, 127.6, 127.5, 127.1, 125.1, 122.5, 122.4, 117.4, 89.8, 78.9, 35.5, 28.5. (c 1.0, MeOH). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 9.40 min; t R (S) = 9.91 min. Characterization data of (R)-12o: colorless oil, 124 mg, 48% yield, 92.6% ee. 1 HNMR(400MHz, CDCl3)δ:7.49(dd,J=7.7,1.7Hz,1H),7.26-7.14(m,3H),7.02-6.92(m,2H),6.85(d,J=8.0Hz,1H),6.69(s,1H ),4.43(t,J=7.5Hz,1H),3.87(dt,J=10.8,5.3Hz,1H),3.66-3.60(m,1H),2.30(s,1H),2.30-2.22(m,1H),2.05-1.96(m,1H). 13 C NMR (100MHz, CDCl3) δ: 153.4, 131.8, 129.1, 128.5, 127.0, 126.9, 126.7, 123.4, 121.5, 116.6, 94.9, 76.4, 60.5, 39.4, 28.9. (c 1.0, MeOH). HPLC conditions: Chiralcel AS-H column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; tR (R) = 11.45 min; t R (S)=13.29min.HRMS(ESI)Calcd for C 15 H 15 O2S([M+H] + ):259.3425,Found:259.3421.

[0148] Example 46:

[0149] Alkyl or substituted alkyl substrates Substrate structures (substrates 13a to 13j) and reaction equations:

[0150]

[0151] The racemic substrate rac-13a (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (R)-13a (45% yield, 92.1% ee) and (S)-14a (45% yield, 87.8% ee). Characterization data of (R)-13a: colorless oil, 73 mg, 45% yield, 92.1% ee. 1 H NMR(400MHz, CDCl3)δ:7.31-7.26(m,1H),7.25-7.22(m,1H),7.14(td,J=7.5,1.3Hz,1H),7.06(dd,J=8.1,1.2H z,1H),3.19(h,J=6.9Hz,1H),2.85(dd,J=15.8,5.5Hz,1H),2.59(dd,J=15.8,7.2Hz,1H),1.35(d,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ: 168.4, 151.3, 128.3, 127.9, 126.6, 124.7, 117.0, 36.9, 29.6, 20.0. (c 1.0,CHCl3).[lit. 16 (c1.0, benzene)] HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 9.11 min; t R (S) = 9.83 min. Characterization data of (S)-14a: colorless oil, 75 mg, 45% yield, 87.8% ee. 1 H NMR (400MHz, CDCl3) δ: 7.25 (dd, J=7.6, 1.6Hz, 1H), 7.15 (td, J=7.9, 1.7Hz, 1H), 7.00 (td, J=7.5, 1.0Hz, 1H), 6.91 (dd, J=8.0,1.1Hz,1H),3.76-3.69(m,1H),3.50-3.42(m,2H),2.09-2.02(m,1H),1.68-1.60(m,1H),1.39(d,J=7.0Hz,3H). 13 C NMR(100MHz, CDCl3)δ:153.7,132.2,127.1,126.8,121.1,115.8,60.8,40.8,27.1,20.9.. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 5.67 min; t R (S)=7.61min.HRMS(ESI)Calcd for C 10 H 15 O2([M+H] + ):167.1067,Found:167.1060.

[0152] Example 47:

[0153] The racemic substrate rac-13b (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (R)-13b (51% yield, 83.4% ee) and (S)-14b (45% yield, 92.0% ee). Characterization data of (R)-13b: colorless oil, 90 mg, 51% yield, 83.4% ee. 1 H NMR (400MHz, CDCl3) δ: 7.32-7.23 (m, 1H), 7.23-7.09 (m, 2H), 7.05 (d, J = 8.1Hz, 1H), 2.94-2.88 (m,J=5.6,4.8Hz,1H),2.79(qd,J=15.6,5.6Hz,2H),1.72-1.55(m,2H),0.96(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ: 168.5, 151.4, 128.3, 128.0, 126.6, 124.3, 117.1, 36.7, 34.5, 27.7, 11.2. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 14.24 min; t R (S) = 17.65 min. Characterization data of (S)-14b: colorless oil, 81 mg, 45% yield, 92.0% ee. 1H NMR (400MHz, CDCl3) δ: 7.12-7.06 (m, 2H), 6.92 (td, J=7.5, 1.3Hz, 1H), 6.84 (dd, J=8.0, 1.3Hz, 1H), 3.70-3.65 (m, 1H), 3.35 (td, J= 10.9,3.5Hz,1H),3.14-3.06(m,1H),2.78(s,1H),2.12-2.04(m,1H),1.82-1.66(m,2H),1.54-1.46(m,1H),0.85(t,J=7.3Hz,3H). 13 C NMR (100MHz, CDCl3) δ: 154.7, 130.5, 127.1, 127.1, 121.3, 116.3, 60.9, 39.1, 34.8, 28.4, 12.5. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 5.67 min; t R (S)=7.61min.HRMS(ESI)Calcd for C 11 H 17 O2([M+H] + ):181.1223,Found:181.1219.

[0154] Example 48:

[0155] The racemic substrate rac-13c (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (R)-13c (yield 52%, 87.4% ee) and (S)-14c (yield 46%, 89.6% ee). Characterization data of (R)-13c: colorless oil, 124 mg, 52% yield, 87.4% ee. 1H NMR (400MHz, CDCl3) δ: 7.35-7.26 (m, 3H), 7.25 (d, J = 3.0Hz, 1H), 7.16-6.96 (m,5H),3.28-3.18(m,1H),2.97(dd,J=13.6,6.5Hz,1H),2.82-2.63(m,3H). 13 C NMR (100MHz, CDCl3) δ: 168.2, 151.4, 138.0, 129.4, 128.7, 128.6, 127.9, 126.9, 126.1, 124.5, 117.2, 41.4, 37.5, 33.9. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 9.31 min; t R (R) = 9.82 min. Characterization data of (S)-14c: colorless oil, 111 mg, 46% yield, 89.6% ee. 1 H NMR(400MHz, CDCl3)δ:7.26-7.12(m,6H),7.09(t,J=6.9Hz,1H),6.93(t,J=7.5Hz,1H),6.82(d,J=8.0Hz,1H),3.63-3.59(m,1H),3.54-3. 47(m,1H),3.34(td,J=10.7,3.8Hz,1H),3.07(dd,J=13.6,6.6Hz,1H),2.96(dd,J=13.6,8.5Hz,1H),2.10-2.01(m,1H),1.64-1.55(m,1H). 13 CNMR(100MHz, CDCl3)δ:154.1,140.7,130.4,129.2,128.3,127.4,126.0,121.2,116.2,60.7,41.8,38.0,34.8. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 11.40 min; t R (R)=20.79min.HRMS(ESI)Calcd for C 16 H19 O2([M+H] + ):243.1380,Found:243.1375.

[0156] Example 49:

[0157] The racemic substrate rac-13d (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-13d (yield 49%, 85.4% ee) and (R)-14d (yield 47%, 96.3% ee). Characterization data of (S)-13d: colorless oil, 93 mg, 49% yield, 85.4% ee. 1 H NMR(400MHz, CDCl3)δ:7.31-7.24(m,1H),7.12-7.15(m,1H),7.13-7.10(m,1H),7.10-7.05(m,1H),2.9 7-2.86(m,1H),2.80-2.69(m,2H),1.86(h,J=6.7Hz,1H),0.97(d,J=6.7Hz,3H),0.92(d,J=6.7Hz,3H). 13 C NMR (100MHz, CDCl3) δ: 169.0, 151.8, 129.1, 128.4, 125.6, 124.2, 117.2, 100.1, 42.0, 32.4, 32.3, 20.3, 19.3. (c 1.0,CHCl3)[lit. 17 (c 1.0, CHCl3)]. HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 11.94 min; t R(S) = 12.59 min. Characterization data of (R)-14d: colorless oil, 91 mg, 47% yield, 96.3% ee. 1 H NMR(400MHz, CDCl3)δ:7.40(s,1H),7.15-7.02(m,2H),6.90(t,J=7.3Hz,1H),6.81(d,J=8.0Hz,1H),3.69-3.50(m,1H),3.26(td,J=10.8,3.5Hz,1 H),3.16(s,1H),2.86(t,J=9.8Hz,1H),2.28-2.20(m,1H),1.96-1.90(m, 1H), 1.49 (t, J = 12.8Hz, 1H), 1.07 (d, J = 6.5Hz, 3H), 0.75 (d, J = 6.6Hz, 3H). 113 C NMR (100MHz, CDCl3) δ: 154.5, 130.6, 127.7, 126.9, 121.1, 115.9, 61.2, 40.4, 36.0, 32.4, 21.8, 21.2. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 9.91 min; t R (R)=12.21min.HRMS(ESI)Calcd for C 12 H 19 O2([M+H] + ):195.1380,Found:195.1378.

[0158] Example 50:

[0159] The racemic substrate rac-13e (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-13e (yield 47%, 87.4% ee) and (R)-14e (yield 48%, 93.7% ee). Characterization data of (S)-13e: colorless oil, 88 mg, 47% yield, 87.4% ee. 1 H NMR(400MHz, CDCl3)δ:7.39(d,J=7.6Hz,1H),7.32-7.26(m,1H),7.14(td,J=7.8,1.3Hz,1H),7.07(dd,J=8.1,1.3Hz,1H),2.91(dd,J=15.7,5.6H z,1H),2.78(dd,J=15.8,7.1Hz,1H),2.42(q,J=7.6Hz,1H),0.94-0.86(m ,1H),0.71-0.56(m,2H),0.33(dq,J=9.6,4.9Hz,1H),0.25-0.18(m,1H). 13 C NMR (100MHz, CDCl3) δ: 168.6, 151.6, 128.6, 127.6, 126.0, 124.5, 117.0, 39.4, 35.7, 15.1, 4.3, 2.9. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 14.45 min; t R (S) = 15.27 min. Characterization data of (R)-14e: colorless oil, 92 mg, 48% yield, 93.7% ee. 1HNMR (400MHz, CDCl3) δ: 7.31 (dd, J=7.6, 1.7Hz, 1H), 7.09 (td, J=7.7, 1.8Hz, 1H), 6.94 (t, J= 7.5Hz,1H),6.81(d,J=7.9Hz,1H),3.75-3.70(m,1H),3.41(td,J=10.6,3.7Hz,1H),2.63(s,1 H),2.36(td,J=10.1,4.7Hz,1H),2.24-2.15(m,1H),1.74-1.66(m,1H),1.20-1.12(m,1H),0. 67-0.61(m,1H),0.46-0.40(m,1H),0.29(dq,J=9.7,4.9Hz,1H),0.08(dq,J=9.8,5.1Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 154.0, 131.4, 127.9, 127.3, 121.2, 116.2, 60.9, 39.2, 38.9, 16.4, 5.9, 4.2. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 11.18 min; t R (S)=12.07min.HRMS(ESI)Calcd for C 12 H 17 O2([M+H] + ):193.1223,Found:193.1219.

[0160] Example 51:

[0161] The racemic substrate rac-13f (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-13f (yield 47%, 91.6% ee) and (R)-14f (yield 50%, 86.1% ee). Characterization data of (S)-13f: colorless oil, 102 mg, 47% yield, 91.6% ee. 1 H NMR(400MHz, CDCl3)δ:7.32-7.16(m,2H),7.15-6.99(m,2H),2.93-2.86(m,1H),2.84-2.73(m ,2H),1.97-1.83(m,2H),1.69-1.64(q,J=10.1Hz,2H),1.59-1.44(m,3H),1.28-1.20(m,2H). 13 C NMR (100MHz, CDCl3) δ: 169.1, 151.8, 129.2, 128.3, 125.7, 124.1, 117.2, 77.5, 77.2, 76.8, 41.9, 41.6, 32.4, 30.7, 29.7, 26.3, 26.2. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 10.56 min; t R (R) = 11.94 min. Characterization data of (R)-14f: colorless oil, 110 mg, 50% yield, 86.1% ee. 1H NMR(400MHz, CDCl3)δ:7.15(d,J=7.6Hz,1H),7.09-7.04(m,1H),6.91(t,J=7.6Hz,1H),6.85-6.82(m,1H),3.69-3.63(m,1H),3.20-3.25(m,1H),2 .95-2.88(m,1H),2.47(s,1H),2.28-2.16(m,2H),2.04-1.96(m,1H),1.7 3-1.66(m,1H),1.63-1.43(m,5H),1.31-1.28(m,1H),0.97-0.83(m,1H). 13 C NMR (100MHz, CDCl3) δ: 154.4, 131.1, 127.9, 126.9, 121.3, 121.3, 116.4, 116.2, 60.9, 45.1, 45.1, 39.5, 38.0, 37.9, 32.2, 25.8, 25.2. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 9.91 min; t R (R)=14.07min.HRMS(ESI)Calcd for C 14 H 21 O2([M+H] + ):221.1536,Found:221.1533.

[0162] Example 52:

[0163] The racemic substrate rac-13g (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford the products (S)-13g (yield 49%, 90.0% ee) and (R)-14g (yield 48%, 92.3% ee). Characterization data of (S)-13g: colorless oil, 113 mg, 49% yield, 90.0% ee. 1 H NMR(400MHz, CDCl3)δ:7.29-7.23(m,1H),7.12(dtd,J=14.7,7.5,1.6Hz,2H),7.05(dd,J=8.1,1.2Hz,1H),2.9 9-2.91(m,1H),2.79-2.68(m,2H),1.83-1.68(m,3H),1.65-1.57(m,2H),1.51-1.41(m,1H),1.22-0.95(m,5H). 13 C NMR (100MHz, CDCl3) δ: 169.1, 151.8, 129.2, 128.3, 125.7, 124.1, 117.2, 41.9, 41.3, 32.4, 30.7, 29.7, 26.3, 26.2. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 21.52 min; t R (R) = 23.00 min. Characterization data of (R)-14g: colorless oil, 112 mg, 48% yield, 92.3% ee. 1H NMR(400MHz, CDCl3)δ:7.15-7.02(m,2H),6.92(t,J=7.4Hz,1H),6.88-6.76(m,1H),6.17(s, 1H),3.66-3.61(m,1H),3.27(td,J=10.6,3.9Hz,1H),2.92-2.86(m,1H),2.31-2.21(m,1H), 2.06(d,J=12.7Hz,1H),1.79(d,J=13.1Hz,1H),1.67-1.55(m,4H),1.52-1.43(m,2H),1.31- 1.23(m,1H),1.17-1.06(m,2H),1.00(qd,J=12.4,3.2Hz,1H),0.80(qd,J=14.4,3.2Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 154.6, 130.4, 127.8, 126.9, 121.3, 116.3, 61.2, 41.9, 39.1, 35.3, 31.9, 31.5, 26.7, 266, 26.5. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 31.51 min; t R (R)=34.34min.HRMS(ESI)Calcd for C 15 H 23 O2([M+H] + ):235.1693,Found:235.1689.

[0164] Example 53:

[0165] The racemic substrate rac-13h (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-13h (yield 49%, 92.5% ee) and (R)-14h (yield 48%, 92.3% ee). Characterization data of (S)-13h: colorless oil, 107 mg, 49% yield, 92.5% ee. 1 H NMR(400MHz, CDCl3)δ:7.12-7.02(m,2H),6.90(dd,J=24.2,7.9Hz,2H),3.88(s,3H),2.93-2.80(m,1H),2.82-2.70(m,1H), 2.38(dt,J=9.0,6.2Hz,1H),0.93-0.83(m,1H),0.68-0.51(m,1H),0.31(dq,J=9.5,4.8Hz,1H),0.19(dq,J=9.5,4.8Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 167.8, 147.6, 140.7, 127.1, 124.4, 119.1, 111.3, 56.1, 39.5, 35.5, 15.1, 4.3, 2.9. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 13.26 min; t R (R) = 17.46 min. Characterization data of (R)-14h: colorless oil, 107 mg, 48% yield, 92.3% ee. 1H NMR (400MHz, CDCl3) δ: 6.92-6.80 (m, 2H), 6.72 (dd, J = 7.8, 1.7Hz, 1H), 6.16 (s, 1H), 3.86 (s, 3H), 3.62-3.56 (m, 1H), 3.46-3.39 (m, 1H), 2.44-2. 38(m,1H),2.17-2.09(m,1H),1.84-1.76(m,1H),1.16-1.07(m,1H),0.6 3-0.54(m,1H),0.40-0.33(m,1H),0.31-0.25(m,1H),0.13-0.07(m,1H). 13 C NMR (100MHz, CDCl3) δ: 146.3, 143.1, 131.1, 120.1, 119.9, 108.3, 60.9, 55.9, 39.6, 39.0, 16.4, 5.7, 4.0. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 8.89 min; t R (R) = 9.59 min.

[0166] Example 54:

[0167] The racemic substrate rac-13i (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-13i (yield 48%, 86.5% ee) and (R)-14i (yield 46%, 90.2% ee). Characterization data of (S)-13i: colorless oil, 105 mg, 48% yield, 86.5% ee. 1H NMR (400MHz, CDCl3) δ: 6.99 (d, J = 8.8 Hz, 1H), 6.92 (d, J = 2.9 Hz, 1H), 6.80 (dd, J=8.8,3.0Hz,1H),3.81(s,3H),2.88(dd,J=15.8,5.5Hz,1H),2.73(dd,J=15.8 ,7.5Hz,1H),2.34(td,J=8.0,5.5Hz,1H),0.93-0.84(m,1H),0.73-0.64(m,1H ),0.63-0.56(m,1H),0.34(dq,J=9.8,5.0Hz,1H),0.22(dq,J=9.8,5.0Hz,1H). 13 C NMR (100MHz, CDCl3) δ: 168.6, 159.9, 152.3, 128.1, 110.4, 102.5, 55.6, 38.5, 35.9, 15.2, 4.1, 2.6. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (S) = 22.88 min; t R (R) = 28.24 min. Characterization data of (R)-14i: colorless oil, 102 mg, 46% yield, 90.2% ee. 1 H NMR (400MHz, CDCl3) δ: 7.20 (d, J=8.5Hz, 1H), 6.53 (dd, J=8.5, 2.5Hz, 1H), 6 .42(q,J=3.2Hz,1H),3.77-3.72(m,4H),3.42(td,J=10.6,3.3Hz,1H),2.29- 2.14(m,2H),1.65(td,J=10.4,3.4Hz,1H),1.26(s,2H),1.16-1.12(m,1H), 0.66-0.62(m,1H),0.47-0.40(m,1H),0.29-0.25(m,1H),0.10-0.04(m,1H). 13 C NMR (100MHz, CDCl3) δ: 158.6, 154.8, 128.4, 123.8, 106.5, 101.9, 60.7, 55.3, 39.0, 38.6, 29.8, 16.5, 5.8, 4.1. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 14.03 min; t R (S)=18.10min.HRMS(ESI)Calcd for C 13 H 19 O2([M+H] + ):223.1329,Found:223.1326.

[0168] Example 55:

[0169] The racemic substrate rac-13j (1.0 mmol), catalyst (R)-4e (1.0 mg, 0.001 mmol), t-BuOK (0.12 g, 1.0 mmol), and MeOH (2.0 mL) were added to a 20 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times and then to 10 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. The reaction mixture was then quenched with 1N HCl (2 mL) and extracted three times with ethyl acetate (5 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10–1:4)) to afford (S)-13j (yield 48%, 89.5% ee) and (R)-14j (yield 48%, 92.3% ee). Characterization data of (S)-13j: colorless oil, 105 mg, 48% yield, 89.5% ee. 1 H NMR (400MHz, CDCl3) δ: 6.99 (d, J=8.8Hz, 1H), 6.92 (dd, J=3.0, 0.9Hz, 1H), 6.80 (dd,J=8.8,3.0Hz,1H),3.81(s,3H),2.88(dd,J=15.8,5.5Hz,1H),2.73(dd,J=1 5.8,7.5Hz,1H),2.34(td,J=8.0,5.5Hz,1H),0.92-0.86(m,1H),0.72-0.65(m,1 H),0.63-0.56(m,1H),0.33(dq,J=9.6,4.9Hz,1H),0.21(dq,J=9.6,4.9Hz,1H). 13C NMR (100MHz, CDCl3) δ: 168.8, 156.3, 145.5, 127.2, 117.7, 113.1, 55.8, 39.6, 35.7, 15.0, 4.5, 2.9. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 14.73 min; t R (S) = 15.34 min. Characterization data of (R)-14j: colorless oil, 107 mg, 48% yield, 92.3% ee. 1 H NMR (400MHz, CDCl3) δ: 6.87 (d, J = 3.0 Hz, 1H), 6.76 (d, J = 8.7 Hz, 1H), 6.6 (dd, J = 8.7, 3. 1Hz,1H),3.77(s,3H),3.74–3.66(m,1H),3.38(td,J=10.7,3.6Hz,1H),2.63(s,1H),2. 34(td,J=10.2,4.6Hz,1H),2.23-2.14(m,1H),1.81(s,1H),1.71-1.63(m,1H),1.17-1. 08(m,1H),0.70-0.58(m,1H),0.49-0.37(m,1H),0.31-0.26(m,1H),0.13-0.05(m,1H). 13 CNMR(100MHz, CDCl3)δ:154.1,148.0,132.8,116.8,113.9,111.7,60.8,55.8,39.3,38.9,16.4,5.9,4.2. (c 1.0, CHCl3). HPLC conditions: chiral column (25 cm × 0.46 cm ID); n-hexane / 2-propanol = 90:10; temperature, room temperature, flow rate = 1.0 mL / min; 220 nm UV detector; t R (R) = 31.51 min; t R (S)=34.34min.HRMS(ESI)Calcd for C 13 H 19 O2([M+H] + ):223.1329,Found:223.1325.

[0170] Example 56:

[0171] The racemic substrate rac-1b (2.38 g, 10.0 mmol), catalyst (S)-4e (10.0 mg, 0.01 mmol), KOtBu (1.21 g, 10.0 mmol), and MeOH (15.0 mL) were added to a 50 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times, then to 20 atm. The reaction mixture was stirred at room temperature (25°C–30°C) until no significant pressure drop was observed. TfOH (2.0 mL) was then added and stirred for 1 hour to quench the reaction. After quenching, the mixture was extracted with ethyl acetate three times (50 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (V / V = 1:10 to 1:4)) to give (R)-1b (1.02 g, yield 43%, 87% ee) and (S)-3b (1.21 g, yield 50%, 91% ee).

[0172] Example 57:

[0173] The racemic substrate rac-1g (2.54 g, 10.0 mmol), catalyst (S)-4e (10.0 mg, 0.01 mmol), KOtBu (1.21 g, 10.0 mmol), and MeOH (15.0 mL) were added to a 50 mL autoclave. The autoclave was pressurized to 5 atm with hydrogen three times, then to 20 atm. The reaction mixture was stirred at room temperature (25°C-30°C) until no significant pressure drop was observed. The reaction mixture was then quenched by the addition of 1N HCl (20.0 mL) and stirred for 1 hour. After quenching, the mixture was extracted three times with ethyl acetate (50 mL). The combined organic phases were washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (V / V = 1:10 to 1:4)) to give (R)-2g (1.43 g, yield 50%, 88% ee) and (S)-3g (1.23 g, yield 48%, 91% ee).

[0174] Example 58:

[0175] The racemic substrate rac-11p (1.10 g, 5.0 mmol), catalyst (S)-4e (5.0 mg, 0.01 mmol), KOtBu (0.61 g, 5.0 mmol), and MeOH (10.0 mL) were added to a 50 mL autoclave. The autoclave was pressurized with hydrogen to 5 atm three times, then to 20 atm. The reaction mixture was stirred at room temperature (25°C-30°C) until no significant pressure drop was observed. 1N HCl (20.0 mL) was then added and stirred for 1 hour to quench the reaction mixture. After quenching, the mixture was extracted with ethyl acetate three times (50 mL x 3). The combined organic phases were washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The concentrate was purified by column chromatography (eluent: ethyl acetate / petroleum ether (v / v = 1:10)) to afford (S)-12p (0.55 g, 50% yield, 90% ee) and (R)-17 (0.81 g, 47% yield, 94% ee). Following the procedures for the synthesis of (S)-16 and (S)-18, (R)-17 (248 mg, 1.0 mmol) was synthesized as a colorless oil (209 mg, 92% yield). 1 H NMR(400MHz, CDCl3)δ:7.49-7.45(m,2H),7.30-7.24(m,2H),3.65(s,3H),3.60(s,3H),4.03-3 .98(m,1H),2.98(dd,J=15.8,5.2Hz,1H),2.82(dd,J=15.8,10.0Hz,1H),1.86(d,J=2.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ: 157.3, 150.9, 129.1, 127.4, 124.8, 123.5, 117.1, 81.4, 75.9, 60.8, 56.1, 36.0, 27.6, 3.7.

Claims

1. A compound of formula A or an enantiomer thereof, characterized in that: The structural formula is: Wherein, R is aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkyl or cyclic alkyl; X 1 , X 2 Identical or different are hydrogen, alkyl, alkoxy, halogen or carboxylate.

2. A compound of formula B or an enantiomer thereof, characterized in that The structural formula is: Among them, R 1 is an aryl group or a substituted aryl group; X 1 , X 2 R may be the same or different and may be hydrogen, alkyl, alkoxy, halogen or carboxylate; 2 For alkyl.

3. The compound according to claim 1 or 2, characterized in that The aryl group is phenyl, thiophene, furan or pyridine; the substituted aryl group is substituted phenyl; the substituted phenyl group is toluene, halobenzene, anisole or phenylpropyl ether.

4. The compound according to claim 1, characterized in that The substituted alkenyl group is: Wherein, D is hydrogen, alkyl, alkoxy or halogen.

5. The compound according to claim 1, characterized in that The substituted alkynyl group is an alkyl group, a cyclic alkyl group, a phenyl group, a thiophene group or Wherein, D is hydrogen, alkyl, alkoxy or halogen.

6. The compound according to any one of claims 1 to 5, characterized in that The structural formula is:

7. A method for the asymmetric catalytic hydrogenation of racemic β-aryl esters or lactones, characterized in that: In the presence of an iridium catalyst with a chiral spirocyclic pyridine aminophosphine ligand and a base, asymmetric catalytic hydrogenation is performed on racemic β-aryl esters or lactones with a hydroxyl group introduced to obtain chiral β-aryl esters and the corresponding chiral γ-aryl primary alcohols with a certain optical purity: Wherein, R is aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkyl or cyclic alkyl; R 2 is an alkyl group; X is hydrogen, an alkyl group, an alkoxy group, a halogen group or a carboxylate group; wherein the chiral spirocyclic pyridine aminophosphine ligand iridium catalyst structural formula is: or an enantiomer thereof, wherein Y is hydrogen or alkyl.

8. The asymmetric catalytic hydrogenation method according to claim 7, characterized in that The racemic β-aryl ester or lactone is a lactone compound, specifically X is hydrogen, alkyl, alkoxy, halogen or carboxylate.

9. The asymmetric catalytic hydrogenation method according to claim 7 or 8, characterized in that When the lactone compound is rac-1, the asymmetric hydrogenation reaction is: X is hydrogen, alkyl, alkoxy, halogen or carboxylate.

10. The asymmetric catalytic hydrogenation method according to claim 7 or 8, characterized in that When the lactone compound is rac-9, the asymmetric hydrogenation reaction is: X is hydrogen, alkyl, alkoxy, halogen or carboxylate.

11. The asymmetric catalytic hydrogenation method according to claim 7 or 8, characterized in that When the lactone compound is rac-11, the asymmetric hydrogenation reaction is: X is hydrogen, alkyl, alkoxy, halogen or carboxylate.

12. The asymmetric catalytic hydrogenation method according to claim 7 or 8, characterized in that When the lactone compound is rac-13, the asymmetric hydrogenation reaction is: X is hydrogen, alkyl, alkoxy, halogen or carboxylate.

13. The asymmetric catalytic hydrogenation method according to any one of claims 7 to 12, characterized in that: The hydrogenation reaction is carried out in the presence of a base, which is an alkali metal salt of alcohol, an alkali metal hydroxide, or an alkali metal carbonate.

14. The asymmetric catalytic hydrogenation method according to any one of claims 7 to 12, characterized in that: The hydrogenation reaction is carried out in the presence of a solvent, and the reaction solvent is one of methanol, ethanol, propanol, isopropanol, butanol, tetrahydrofuran, toluene, methyl tert-butyl ether, dioxane, DMF, DMSO, or a mixed solvent of several thereof.

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