Method for directly constructing highly optically active tetrasubstituted allenic acid compounds

Abstract

The present invention discloses a method for directly constructing highly optically active tetrasubstituted allenic acid compounds, i.e., a one-step process for directly constructing highly optically active axially chiral tetrasubstituted allenic acid compounds by using tertiary propargyl alcohol, carbon monoxide and water as reactants in an organic solvent in the presence of palladium catalyst, chiral diphosphine ligand, monophosphine ligand and organic phosphoric acid. The method of the present invention has the following advantages: operations are simple, raw materials and reagents are readily available, the reaction conditions are mild, the substrate has high universality, the functional group has good compatibility, and the reaction has high enantioselectivity (90%˜>99% ee). The highly optically active allenic acid compounds obtained by the present invention can be used as an important intermediate to construct γ-butyrolactone compounds containing tetrasubstituted chiral quaternary carbon centers, tetrasubstituted allenic alcohol and other compounds.

Claims

1. A method for preparing optically active axially chiral allenic acid compounds of formula 2 with greater than 90% enantiomeric excess, wherein, in the presence of palladium catalyst, chiral diphosphine ligand, monophosphine ligand and organic phosphoric acid, a tertiary propargyl alcohol with different substituents, carbon monoxide and water undergo asymmetric allylation reaction in an organic solvent through transition metal catalysis, preparing the optically active axially chiral allenic acid compounds in one-step synthesis, the reaction process has the following reaction equation (I): ##STR00053## the different substituents of the tertiary propargyl alcohol with different substituents are R.sup.1, R.sup.2, R.sup.3; wherein, R.sup.1 is an alkyl, an alkyl with functional group, phenyl, aryl, heterocyclic group or naphthyl; R.sup.2 is an alkyl, an alkyl with functional group, phenyl, aryl, heterocyclic group or naphthyl; R.sup.3 is an alkyl, an alkyl with functional group, phenyl, aryl, heterocyclic group or naphthyl; the said aryl is a phenyl with electron-donating or electron-withdrawing substituents at the ortho, meta, and para positions; the said heterocyclic group is thienyl, furyl, or pyridyl with electron-donating or electron-withdrawing substituents.

2. The method of claim 1, wherein, R.sup.1 is a C1-C20 alkyl, a C1-C20 alkyl with functional group at the end, phenyl, aryl, heterocyclic group or naphthyl; R.sup.2 is a C1-C10 alkyl, a C1-C10 alkyl with functional group at the end, phenyl, aryl, heterocyclic group or naphthyl; R.sup.3 is a C1-C10 alkyl, a C1-C10 alkyl with a functional group at the end, phenyl, aryl, heterocyclic group or naphthyl; wherein, the functional group of the C1-C20 alkyl or C1-C10 alkyl with a functional group at the end, is selected from the group consisting of carbon-carbon double bond, carbon-carbon triple bond, ester group, hydroxyl group, acyl group, acyloxy group, amide group, halogen, carboxyl group, or cyano group; the aryl is a phenyl with electron-withdrawing or electron-donating substituents at the ortho, meta, and para positions; the heterocyclic group is thienyl, furyl, naphthyl or pyridyl, with electron-withdrawing or electron-donating substituents; the electron-withdrawing substituent is halogen, nitro group, ester group, carboxyl group, acyl group, amide group, cyano group; the electron-donating substituent is alkyl, alkenyl, phenyl, alkoxy group, hydroxyl, or amino group.

3. The method of claim 1, wherein, the method comprises the following steps: 1) a palladium catalyst, a chiral diphosphine ligand, a monophosphine ligand and an organic phosphoric acid are added in sequence into a dried reaction tube, plugging the reaction tube with a rubber stopper, connecting a vacuum pump, degassing the reaction tube and refilling with argon three times, adding the tertiary propargyl alcohol, water, and a certain volume of organic solvent; freezing the reaction tube in liquid nitrogen bath, inserting carbon monoxide balloon into the dried reaction tube, degassing to remove the argon inside completely, and refilling with CO by the balloon of CO three times, returning the reaction system to room temperature, putting the reaction tube in the preset low-temperature bath or oil bath at −20-60° C. and stirring for 4-36 hours; wherein the amount of the organic solvent is 1.0-10.0 mL to 1 mmol of tertiary propargyl alcohol; 2) after the completion of the reaction in step (1), raising the reaction tube from the low-temperature bath; after returning to the room temperature, ethyl acetate is added into the reaction tube and a mixture obtained, filtering the mixture with silica gel short column, washing with a certain amount of ethyl acetate, concentrating, and subjecting to the flash column chromatography, so as to obtain the optically active axially chiral allenic acid compounds; wherein the amount of ethyl acetate is 1.0-100 mL to 1 mmol of tertiary propargyl alcohol (+1).

4. The method of claim 1, wherein the palladium catalysts are any one or more of dis-(allyl-palladium chloride), tetra-(triphenylphosphine) palladium, tri-(dibenzylidene-acetone) dipalladium, dis-(cinnamyl-palladium chloride), dis-(dibenzylidene-acetone) monopalladium, palladium chloride, palladium acetate, dis-(triphenylphosphine) palladium chloride and bis-(acetonitrile) palladium chloride.

5. The method of claim 1, wherein the chiral diphosphine ligand is selected from the group consisting of (R)-L2-(R)-L4 and its enantiomer (S)-L2-(S)-L4 in the following structures; wherein, “Ar” is a phenyl, an aryl, heterocyclic group or naphthyl; the aryl is a phenyl substituted by alkyl and/or alkoxy group at the ortho, meta, and para positions; the heterocyclic group is thienyl, furyl, naphthyl or pyridyl substituted by alkyl or alkoxy group, furan substituted by alkyl or alkoxy group, pyridine substituted by alkyl or alkoxy group; ##STR00054##

6. The method of claim 5, wherein the chiral diphosphine ligand is selected from (R)-L4 and its enantiomer (S)-L4, the said structure of (R)-L4 is as follows: wherein, “Ar” is 3,5-dialkyl-4-alkoxyphenyl, 3,5-dialkylphenyl or phenyl; ##STR00055##

7. The method of claim 1, wherein the monophosphine ligands are selected from the group consisting of tributylphosphine, tricyclohexylphosphine, triphenylphosphine, tris(ortho-methyl-phenyl)phosphine, tris(meta-methyl-phenyl) phosphine, tris(para-methyl-phenyl)phosphine, tris(para-methoxyphenyl)phosphine, tris(3,5-di-tri-fluoromethyl-phenyl) phosphine, and trifuryl-phosphine; and/or, the organic solvents are selected from the group consisting of N-methyl pyrrolidone, 1,4-dioxane, tetrahydrofuran, acetonitrile, methyl tert-butyl ether, chlorobenzene, toluene, trifluorotoluene, dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroform, and acetic acid.

8. The method of claim 1, wherein the organic phosphoric acid is selected from any one or more of organic phosphoric acid 1, organic phosphoric acid 2, organic phosphoric acid 3, the structure of which is as follows; wherein, R.sup.1 is hydrogen, C1-C6 alkyl, phenyl or aryl; the said aryl is a phenyl substituted by C1-C6 alkyl at the ortho, meta, and para positions; R.sup.2 is C1-C6 alkyl, phenyl or aryl; the said aryl is a phenyl substituted by C1-C6 alkyl at the ortho, meta, and para positions, ##STR00056## organic phosphoric acid 1, organic phosphoric acid 2, organic phosphoric acid 3.

9. The method of claim 1, wherein the molar ratio of tertiary propargyl alcohol (±1) with different substituents, water, palladium catalyst, chiral diphosphine ligand, monophosphine ligand and organic phosphoric acid in equation (I) of the present invention is 1.0: (1.0-30.0): (0.005-0.1): (0.005-0.1): (0.01-0.3): (0.01-0.3); and/or, the reaction temperature of the invention is 20-60° C.; and/or, the dosage of the organic solvent is 1.0-10.0 mL to 1 mmol of tertiary propargyl alcohol.

10. The method of claim 2, wherein the palladium catalysts are any one or more of dis-(allyl-palladium chloride), tetra-(triphenylphosphine) palladium, tri-(dibenzylidene-acetone) dipalladium, dis-(cinnamyl-palladium chloride), dis-(dibenzylidene-acetone) monopalladium, palladium chloride, palladium acetate, dis-(triphenylphosphine) palladium chloride and bis-(acetonitrile) palladium chloride.

11. The method of claim 3, wherein the palladium catalysts are any one or more of dis-(allyl-palladium chloride), tetra-(triphenylphosphine) palladium, tri-(dibenzylidene-acetone) dipalladium, dis-(cinnamyl-palladium chloride), dis-(dibenzylidene-acetone) monopalladium, palladium chloride, palladium acetate, dis-(triphenylphosphine) palladium chloride and bis-(acetonitrile) palladium chloride.

12. The method of claim 2, wherein the chiral diphosphine ligand is selected from one or more of (R)-L2-(R)-L4 or its enantiomer (S)-L2-(S)-L4 in the following structures; wherein, “Ar” is a phenyl, an aryl, heterocyclic group or naphthyl; the aryl is a phenyl substituted by alkyl and/or alkoxy group at the ortho, meta, and para positions; the heterocyclic group is thienyl, furyl, naphthyl or pyridyl substituted by alkyl or alkoxy group, furan substituted by alkyl or alkoxy group, pyridine substituted by alkyl or alkoxy group; ##STR00057##

13. The method of claim 3, wherein the chiral diphosphine ligand is selected from one or more of (R)-L2-(R)-L4 or its enantiomer (S)-L2-(S)-L4 in the following structures; wherein, “Ar” is a phenyl, an aryl, heterocyclic group or naphthyl; the aryl is a phenyl substituted by alkyl and/or alkoxy group at the ortho, meta, and para positions; the heterocyclic group is thienyl, furyl, naphthyl or pyridyl substituted by alkyl or alkoxy group, furan substituted by alkyl or alkoxy group, pyridine substituted by alkyl or alkoxy group; ##STR00058##

14. The method of claim 2, wherein the monophosphine ligands are selected from the group consisting of tributylphosphine, tricyclohexylphosphine, triphenylphosphine, tris(ortho-methyl-phenyl)phosphine, tris(meta-methyl-phenyl) phosphine, tris(para-methyl-phenyl)phosphine, tris(para-methoxyphenyl)phosphine, tris(3,5-di-tri-fluoromethyl-phenyl) phosphine, trifuryl-phosphine; and, the organic solvents are selected from the group consisting of N-methyl pyrrolidone, 1,4-dioxane, tetrahydrofuran, acetonitrile, methyl tert-butyl ether, chlorobenzene, toluene, trifluorotoluene, dichloromethane, 1, 1-dichloroethane, 1,2-dichloroethane, chloroform, and acetic acid.

15. The method of claim 3, wherein the monophosphine ligands are selected from the group consisting of tributylphosphine, tricyclohexylphosphine, triphenylphosphine, tris(ortho-methyl-phenyl)phosphine, tris(meta-methyl-phenyl) phosphine, tris(para-methyl-phenyl)phosphine, tris(para-methoxyphenyl)phosphine, tris(3,5-di-tri-fluoromethyl-phenyl) phosphine, and trifuryl-phosphine; and/or, the organic solvents are selected from the group consisting of N-methyl pyrrolidone, 1,4-dioxane, tetrahydrofuran, acetonitrile, methyl tert-butyl ether, chlorobenzene, toluene, trifluorotoluene, dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroform, and acetic acid.

16. The method of claim 2, wherein the organic phosphoric acid is selected from any one or more of organic phosphoric acid 1, organic phosphoric acid 2, organic phosphoric acid 3, the structure of which is as follows; wherein, R.sup.1 is hydrogen, C1-C6 alkyl, phenyl or aryl; the said aryl is a phenyl substituted by C1-C6 alkyl at the ortho, meta, and para positions; R.sup.2 is C1-C6 alkyl, phenyl or aryl; the said aryl is a phenyl substituted by C1-C6 alkyl at the ortho, meta, and para positions, ##STR00059## organic phosphoric acid 1, organic phosphoric acid 2, organic phosphoric acid 3.

17. The method of claim 3, wherein the organic phosphoric acid is selected from any one or more of organic phosphoric acid 1, organic phosphoric acid 2, organic phosphoric acid 3, the structure of which is as follows; wherein, R.sup.1 is hydrogen, C1-C6 alkyl, phenyl or aryl; the said aryl is a phenyl substituted by C1-C6 alkyl at the ortho, meta, and para positions; R.sup.2 is C1-C6 alkyl, phenyl or aryl; the said aryl is a phenyl substituted by C1-C6 alkyl at the ortho, meta, and para positions, ##STR00060## organic phosphoric acid 1, organic phosphoric acid 2, organic phosphoric acid 3.

Description

PREFERRED EMBODIMENTS OF THE INVENTION

(1) The following examples are given to further illustrating the specific solutions of the present invention. The process, conditions, experimental methods, and so on for implementing the present invention are all general knowledge and common knowledge in the field except for the contents specifically mentioned below, and the present invention has no special limitation. The specific structural formula and the corresponding number of chiral diphosphine ligands involved in all the examples are as follows:

(2) ##STR00007##

Example 1

(3) ##STR00008##

(4) wherein, “mol” refers to mole, “toluene” refers to toluene, “CO balloon” refers to carbon monoxide balloon, “ee” refers to the percentage of enantiomeric excess.

(5) PdCl.sub.2 (0.0036 g, 0.02 mmol), chiral diphosphine ligand (R)-L4c (0.057 g, 0.048 mmol), monophosphine ligand PPh.sub.3 (0.0527 g, 0.2 mmol), and (PhO).sub.2PO.sub.2H (0.0501 g, 0.2 mmol) were added to a dried Schlenk reaction tube. The reaction tube was then plugged with a rubber stopper, and then connected with the vacuum pump, and replaced the argon three times under argon atmosphere. And under the protection of the argon, tertiary propargyl alcohol (±)-1a (0.2016 g, 1 mmol), toluene (3 mL), water (360 μL, d=1.0 g/ml, 0.36 g, 20 mmol) and toluene (2 ml) were added. After closed the argon, freezed the reaction tube in liquid nitrogen bath for 3 minutes, inserted carbon monoxide balloon (about 1 liter), replaced carbon monoxide under the atmosphere of carbon monoxide three times, then removed the liquid nitrogen bath. When the reaction system returned to the room temperature and melted into liquid, putted the reaction tube in the preset −5° C. low temperature bath and stirred for 18 hours. The reaction tube was took out of the low temperature bath, and returned to the room temperature and added H.sub.2O.sub.2 (40 μL, d=1.13 g/mL, 30 wt. % in H.sub.2O, 0.0135 g, 0.4 mmol), stirred at room temperature for 30 minutes. The reaction solution was diluted with ethyl acetate (5 mL), the mixture solution was filtered with silica gel short column (3 cm), and then washed with ethyl acetate (20 mL), concentrated, and subjected to the flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.1033 g, 45%): solid; 93% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=7.9 min, t.sub.R (minor)=10.0 min); [α].sub.D.sup.26=+21.2 (c=1.10, CHCl.sub.3). Melting point: 88.4-90.1° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, d.sub.6-DMSO): δ=12.41 (s, 1H, COOH), 7.44-7.32 (m, 4H, Ar—H), 7.32-7.22 (m, 1H, Ar—H), 2.24 (t, J=7.4 Hz, 2H, CH.sub.2), 2.12 (s, 3H, CH.sub.3), 1.46-1.22 (m, 4H, 2×CH.sub.2), 0.84 (t, J=7.0 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, d.sub.6-DMSO): δ=210.4, 167.9, 135.2, 128.7, 127.5, 125.8, 103.6, 101.9, 29.9, 28.2, 21.8, 16.3, 13.8; IR (neat): ν=3210-2410 (br), 1935, 1678, 1416, 1279, 1061 cm.sup.−1; MS (70 eV, EI) m/z (%): 230 (M.sup.+, 3.01), 143 (100); Anal. Calcd. for C.sub.15H.sub.18O.sub.2: C, 78.23, H, 7.88; found: C, 78.03, H, 7.94.

Example 2

(6) ##STR00009##

(7) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.0564 g, 0.048 mmol), PPh.sub.3 (0.0523 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.05 g, 0.2 mmol), (±)-1b (0.2157 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2b (0.1029 g, 42%): oil substance; 96% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=6.5 min, t.sub.R (minor)=9.3 min); [α].sub.D.sup.26=+106.7 (c=1.50, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.29-7.22 (m, 1H, Ar—H), 7.22-7.12 (m, 3H, Ar—H), 2.40 (s, 3H, CH.sub.3), 2.35-2.05 (m, 5H, CH.sub.2 and CH.sub.3), 1.55-1.40 (m, 2H, CH.sub.2), 1.40-1.27 (m, 2H, CH.sub.2), 0.90 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=210.2, 173.8, 136.2, 136.0, 130.6, 127.9, 127.6, 125.9, 104.5, 98.9, 30.1, 28.1, 22.2, 20.4, 19.9, 13.8; IR (neat): ν=3200-2410 (br), 1947, 1674, 1415, 1274, 1041 cm.sup.−1; MS (70 eV, EI) m/z (%): 245 (M.sup.++1, 2.27), 244 (M.sup.+, 11.75), 143 (100); HRMS calcd for C.sub.16H.sub.20O.sub.2 [M.sup.+]: 244.1463, found: 244.1467.

Example 3

(8) ##STR00010##

(9) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.0571 g, 0.048 mmol), PPh.sub.3 (0.0526 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0499 g, 0.2 mmol), (±)-1c (0.2165 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at −5° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2c (0.0687 g, 28%): solid; 94% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=6.5 min, t.sub.R (minor)=7.8 min); [α].sub.D.sup.26=+16.5 (c=1.00, CHCl.sub.3). Melting point: 96.8-98.5° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.27-7.20 (m, 1H, Ar—H), 7.20-7.15 (m, 2H, Ar—H), 7.07 (d, J=7.2 Hz, 1H, Ar—H), 2.40-2.28 (m, 5H, CH.sub.2 and CH.sub.3), 2.18 (s, 3H, CH.sub.3), 1.51-1.41 (m, 2H, CH.sub.2), 1.41-1.28 (m, 2H, CH.sub.2), 0.88 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.6, 172.8, 138.1, 134.9, 128.42, 128.37, 126.7, 123.2, 105.2, 101.6, 30.2, 28.3, 22.3, 21.5, 16.4, 13.8; IR (neat): ν=3250-2400 (br), 1932, 1674, 1418, 1276, 1063 cm.sup.−1; MS (70 eV, EI) m/z (%): 245 (M.sup.++1, 3.90), 244 (M.sup.+, 9.06), 157 (100); Anal. Calcd. for C.sub.16H.sub.20O.sub.2: C, 78.65, H, 8.25; found C, 78.57, H, 8.21.

Example 4

(10) ##STR00011##

(11) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0037 g, 0.02 mmol), (R)-L4c (0.0569 g, 0.048 mmol), PPh.sub.3 (0.0525 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.05 g, 0.2 mmol), (±)-1d (0.2175 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at −5° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2d (0.0909 g, 37%): solid; 90% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=7.9 min, t.sub.R(minor)=8.5 min); [α].sub.D.sup.26=+15.8 (c=1.00, CHCl.sub.3). Melting point: 109.3-111.1° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.26 (d, J=8.0 Hz, 2H, Ar—H), 7.14 (d, J=7.6 Hz, 2H, Ar—H), 2.40-2.25 (m, 5H, CH.sub.2 and CH.sub.3), 2.17 (s, 3H, CH.sub.3), 1.54-1.40 (m, 2H, CH.sub.2), 1.40-1.27 (m, 2H, CH.sub.2), 0.87 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.5, 173.1, 137.4, 132.0, 129.2, 126.0, 105.0, 101.7, 30.2, 28.3, 22.2, 21.1, 16.3, 13.8; IR (neat): ν=3210-2400 (br), 1936, 1673, 1417, 1278, 1066 cm.sup.−1; MS (70 eV, EI) m/z (%): 245 (M.sup.++1, 10.17), 244 (M.sup.+, 6.23), 157 (100); Anal. Calcd. for C.sub.16H.sub.20O.sub.2: C, 78.65, H, 8.25; found C, 78.65, H, 8.22.

Example 5

(12) ##STR00012##

(13) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.0566 g, 0.048 mmol), PPh.sub.3 (0.0524 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0504 g, 0.2 mmol), (±)-1e (0.2324 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at −5° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=20/1/1) to afford a product: chiral allenic acid (S)-2e (0.0963 g, 37%): solid; 91% ee (HPLC conditions: AS-H column, hexane/i-PrOH=95/5, 1.3 mL/min, λ=214 nm, t.sub.R (major)=4.7 min, t.sub.R (minor)=5.8 min); [α].sub.D.sup.27=+16.8 (c=1.11, CHCl.sub.3). Melting point: 58.5-60.0° C. (petroleum ether/dichloromethane recrystallization). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.26 (t, J=8.0 Hz, 1H, Ar—H), 7.03-6.88 (m, 2H, Ar—H), 6.80 (dd, J.sub.1=8.0 Hz, J.sub.2=2.0 Hz, 1H, Ar—H), 3.80 (s, 3H, OCH.sub.3), 2.32 (t, J=7.4 Hz, 2H, CH.sub.2), 2.18 (s, 3H, CH.sub.3), 1.55-1.27 (m, 4H, 2×CH.sub.2), 0.88 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.6, 172.8, 159.7, 136.5, 129.5, 118.6, 112.8, 112.0, 105.1, 101.8, 55.2, 30.2, 28.3, 22.2, 16.3, 13.2; IR (neat): ν=3200-2410 (br), 1936, 1679, 1465, 1417, 1374, 1320, 1283, 1204, 1175, 1122, 1084, 1047, 1032, 1010 cm.sup.−1; MS (70 eV, EI) m/z (%): 261 (M.sup.++1, 2.06), 260 (M.sup.+, 11.47), 173 (100); HRMS: Calcd for C.sub.16H.sub.20O.sub.3 (M.sup.+): 260.1407; Found: 260.1402.

Example 6

(14) ##STR00013##

(15) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.0564 g, 0.048 mmol), PPh.sub.3 (0.053 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0505 g, 0.2 mmol), (±)-1f (0.2356 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at −5° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2f (0.1086 g, 41%): solid; 94% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=8.4 min, t.sub.R (minor)=10.4 min); [α].sub.D.sup.26=+37.8 (c=1.20, CHCl.sub.3). Melting point: 110.4-111.7° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.30 (s, 4H, Ar—H), 2.32 (t, J=7.4 Hz, 2H, CH.sub.2), 2.16 (s, 3H, CH.sub.3), 1.50-1.40 (m, 2H, CH.sub.2), 1.40-1.28 (m, 2H, CH.sub.2), 0.88 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.5, 172.9, 133.6, 133.4, 128.7, 127.3, 104.4, 102.2, 30.2, 28.2, 22.2, 16.3, 13.8; IR (neat): ν=3200-2410 (br), 1936, 1672, 1416, 1281, 1089 cm.sup.−1; MS (70 eV, EI) m/z (%): 266 (M.sup.+(.sup.37Cl), 2.09), 264 (M.sup.+(.sup.35Cl), 4.20), 177 (100); Anal. Calcd. for C.sub.15H.sub.17ClO.sub.2: C, 68.05, H, 6.47; found C, 67.95, H, 6.43.

Example 7

(16) ##STR00014##

(17) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.0578 g, 0.048 mmol), PPh.sub.3 (0.0525 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.05 g, 0.2 mmol), (±)-1g (0.2813 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at −5° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=5/1) to afford a product: chiral allenic acid (S)-2g (0.0928 g, 30%): solid; 92% ee (HPLC conditions: AS-H column, hexane/i-PrOH=95/5, 0.9 mL/min, λ=214 nm, t.sub.R (major)=6.2 min, t.sub.R (minor)=7.7 min); [α].sub.D.sup.26=+25.0 (c=1.01, CHCl.sub.3). Melting point: 125.1-126.0° C. (petroleum ether/dichloromethane recrystallization). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.46 (d, J=8.4 Hz, 2H, Ar—H), 7.23 (d, J=8.4 Hz, 2H, Ar—H), 2.32 (d, J=7.4 Hz, 2H, CH.sub.2), 2.17 (s, 3H, CH.sub.3), 1.52-1.29 (m, 4H, 2×CH.sub.2), 0.88 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.4, 172.2, 134.1, 131.7, 127.6, 121.6, 104.5, 102.2, 30.2, 28.3, 22.2, 16.2, 13.8; IR (neat): ν=3200-2400 (br), 1940, 1685, 1416, 1280, 1075 cm.sup.−1; MS (70 eV, EI) m/z (%): 310 (M.sup.+(.sup.81Br), 1.97), 308 (M.sup.+(.sup.79Br), 1.84), 142 (100); HRMS calcd for C.sub.15H.sub.17O.sub.2.sup.81Br [M.sup.+]: 310.0387, found: 310.0370.

Example 8

(18) ##STR00015##

(19) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0037 g, 0.02 mmol), (R)-L4c (0.0571 g, 0.048 mmol), PPh.sub.3 (0.0527 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.05 g, 0.2 mmol), (±)-1h (0.2607 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=20/1/1, petroleum ether (60˜90° C.)/ethyl acetate=7/1) to afford a product: chiral allenic acid (S)-2h (0.1013 g, 35%): solid; 97% ee (HPLC conditions: AS-H column, hexane/i-PrOH=90/10, 1.0 mL/min, λ=214 nm, t.sub.R(minor)=6.2 min, t.sub.R(major)=7.7 min); [α].sub.D.sup.26=+22.1 (c=1.00, CHCl.sub.3). Melting point: 125.3-127.5° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=8.00 (d, J=8.4 Hz, 2H, Ar—H), 7.44 (d, J=8.4 Hz, 2H, Ar—H), 3.92 (s, 3H, OCH.sub.3), 2.34 (t, J=7.4 Hz, 2H, CH.sub.2), 2.21 (s, 3H, CH.sub.3), 1.52-1.40 (m, 2H, CH.sub.2), 1.40-1.28 (m, 2H, CH.sub.2), 0.88 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=213.1, 172.4, 166.8, 139.9, 129.8, 129.0, 125.9, 104.7, 102.3, 52.1, 30.1, 28.2, 22.2, 16.2, 13.8; IR (neat): ν=3250-2400 (br), 1938, 1680, 1423, 1270, 1107 cm.sup.−1; MS (70 eV, EI) m/z (%): 289 (M.sup.++1, 2.11), 288 (M.sup.+, 10.34), 143 (100); Anal. Calcd. for C.sub.17H.sub.20O.sub.4: C, 70.81, H, 6.99; found C, 70.67, H, 7.13.

Example 9

(20) ##STR00016##

(21) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0035 g, 0.02 mmol), (R)-L4c (0.0578 g, 0.048 mmol), PPh.sub.3 (0.0524 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.05 g, 0.2 mmol), (±)-1i (0.2523 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1-10/1/1) to afford a product: chiral allenic acid (S)-2i (0.1037 g, 37%): solid; 92% ee (HPLC conditions: AS-H column, hexane/i-PrOH=95/5, 1.3 mL/min, λ=214 nm, t.sub.R(major)=4.5 min, t.sub.R(minor)=5.6 min); [α].sub.D.sup.27=−9.2 (c=1.02, CHCl.sub.3). Melting point: 137.5-138.4° C. (petroleum ether/ethyl acetate). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.94-7.61 (m, 4H, Ar—H), 7.62-7.30 (m, 3H, Ar—H), 2.60-2.08 (m, 5H, CH.sub.3 and CH.sub.3), 1.64-1.29 (m, 4H, 2×CH.sub.2), 0.88 (t, J=7.0 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=213.2, 172.6, 133.5, 132.8, 132.4, 128.10, 128.06, 127.6, 126.3, 126.1, 124.8, 124.2, 105.5, 102.1, 30.2, 28.4, 22.3, 16.3, 13.8; IR (neat): ν=3200-2410 (br), 1936, 1680, 1412, 1277, 1247 cm.sup.−1; MS (70 eV, EI) m/z (%): 281 (M.sup.++1, 4.05), 280 (M.sup.+, 15.75), 193 (100); Anal. Calcd. for C.sub.19H.sub.20O.sub.2: C, 81.40, H, 7.19; found C, 81.45, H, 7.20.

Example 10

(22) ##STR00017##

(23) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.0571 g, 0.048 mmol), PPh.sub.3 (0.0524 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.05 g, 0.2 mmol), (±)-1j (0.2086 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at −5° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2j (0.1037 g, 37%): solid; 92% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=10.5 min, t.sub.R(minor)=13.2 min); [α].sub.D.sup.27=+11.5 (c=1.00, CHCl.sub.3). Melting point: 82.6-83.8° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.28 (d, J=4.8 Hz, 1H, one proton from thieny), 7.16 (d, J=2.8 Hz, 1H, one proton from thieny), 7.04 (d, J=4.8 Hz, 1H, one proton from thieny), 2.31 (t, J=7.6 Hz, 2H, CH.sub.2), 2.17 (s, 3H, CH.sub.3), 1.52-1.41 (m, 2H, CH.sub.2), 1.40-1.29 (m, 2H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.8, 172.3, 136.5, 126.3, 125.9, 120.6, 101.4, 101.3, 30.2, 28.4, 22.3, 16.7, 13.8; IR (neat): ν=3200-2410 (br), 1936, 1673, 1417, 1279, 1079 cm.sup.−1; MS (70 eV, EI) m/z (%): 237 (M.sup.++1, 1.29), 236 (M.sup.+, 7.96), 149 (100); Anal. Calcd. for C.sub.13H.sub.16O.sub.2S: C, 66.07, H, 6.82; found C, 65.93, H, 6.70.

Example 11

(24) ##STR00018##

(25) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.057 g, 0.048 mmol), PPh.sub.3 (0.0524 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0501 g, 0.2 mmol), (±)-1k (0.1831 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2k (0.076 g, 36%): oil substance; 99% ee (HPLC conditions: AD-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (minor)=6.9 min, t.sub.R(major)=7.4 min); [α].sub.D.sup.27=+38.5 (c=1.36, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=2.25-2.13 (m, 2H, CH.sub.2), 1.77 (s, 3H, CH.sub.3), 1.45-1.29 (m, 4H, 2×CH.sub.2), 1.10 (s, 9H, 3×CH.sub.3), 0.90 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=208.0, 173.9, 113.0, 99.4, 34.2, 30.3, 28.8, 28.0, 22.3, 14.0, 13.9; IR (neat): ν=3210-2400 (br), 1946, 1669, 1412, 1274, 1240, 1114 cm.sup.−1; MS (ESI) m/z: 211 (M.sup.+H+); HRMS calcd for C.sub.13H.sub.23O.sub.2 [M+H.sup.+]: 211.1693, found: 211.1692.

Example 12

(26) ##STR00019##

(27) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.0569 g, 0.048 mmol), PPh.sub.3 (0.0526 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0495 g, 0.2 mmol), (±)-1l (0.2175 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2l (0.0984g, 40%): solid; 93% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=7.4 min, t.sub.R(minor)=11.5 min); [α].sub.D.sup.27=+11.2 (c=1.00, CHCl.sub.3). Melting point: 93.2-93.6° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.45-7.29 (m, 4H, Ar—H), 7.29-7.20 (m, 1H, Ar—H), 2.32 (t, J=7.6 Hz, 2H, CH.sub.2), 2.19 (s, 3H, CH.sub.3), 1.58-1.38 (m, 2H, CH.sub.2), 1.36-1.16 (m, 4H, 2×CH.sub.2), 0.84 (t, J=6.6 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.6, 173.1, 135.0, 128.5, 127.5, 126.0, 105.1, 101.8, 31.3, 28.5, 27.7, 22.4, 16.3, 14.0; IR (neat): ν=3200-2410 (br), 1937, 1675, 1413, 1275, 1064, 1023 cm.sup.−1; MS (70 eV, EI) m/z (%): 244 (M.sup.+, 3.21), 143 (100); Anal. Calcd. for C.sub.16H.sub.20O.sub.2: C, 78.65, H, 8.25; found C, 78.68, H, 8.38.

Example 13

(28) ##STR00020##

(29) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0037 g, 0.02 mmol), (R)-L4c (0.057 g, 0.048 mmol), PPh.sub.3 (0.0524 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0501 g, 0.2 mmol), (±)-1m (0.2298 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2m (0.1081 g, 42%): solid; 90% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=6.6 min, t.sub.R (minor)=9.4 min); [α].sub.D.sup.26=+7.4 (c=1.20, CHCl.sub.3). Melting point: 76.9-78.1° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.46-7.30 (m, 4H, Ar—H), 7.30-7.21 (m, 1H, Ar—H), 2.32 (t, J=7.4 Hz, 2H, CH.sub.2), 2.19 (s, 3H, CH.sub.3), 1.53-1.41 (m, 2H, CH.sub.2), 1.38-1.11 (m, 6H, 3×CH.sub.2), 0.84 (t, J=6.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.6, 173.0, 135.0, 128.5, 127.5, 126.1, 105.2, 101.8, 31.6, 28.8, 28.6, 28.0, 22.6, 16.3, 14.0; IR (neat): ν=3250-2410 (br), 1936, 1679, 1417, 1272, 1026 cm.sup.−1; MS (70 eV, EI) m/z (%): 258 (M.sup.+, 3.96), 143 (100); Anal. Calcd. for C.sub.17H.sub.22O.sub.2: C, 79.03, H, 8.58; found C, 78.86, H, 8.62.

Example 14

(30) ##STR00021##

(31) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0037 g, 0.02 mmol), (R)-L4c (0.0567 g, 0.048 mmol), PPh.sub.3 (0.0526 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0501 g, 0.2 mmol), (±)-1n (0.2578 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2n (0.1144 g, 40%): oil substance; 98% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.0 min, t.sub.R(minor)=9.0 min); [α].sub.D.sup.27=+69.4 (c=1.34, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.29-7.22 (m, 1H, Ar—H), 7.20-7.12 (m, 3H, Ar—H), 2.40 (s, 3H, CH.sub.3), 2.35-2.15 (m, 2H, CH.sub.2), 2.13 (s, 3H, CH.sub.3), 1.54-1.41 (m, 2H, CH.sub.2), 1.35-1.15 (m, 8H, 4×CH.sub.2), 0.87 (t, J=6.8 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=210.2, 173.8, 136.2, 136.0, 130.6, 127.9, 127.5, 125.9, 104.5, 98.9, 31.8, 29.11, 29.05, 28.3, 28.0, 22.6, 20.4, 19.9, 14.1; IR (neat): ν=3220-2410 (br), 1948, 1675, 1414, 1274, 1043 cm.sup.−1; MS (70 eV, EI) m/z (%): 287 (M.sup.++1, 2.48), 286 (M.sup.+, 11.23), 143 (100); HRMS calcd for C.sub.19H.sub.26O.sub.2 [M.sup.+]: 286.1933, found: 286.1930.

Example 15

(32) ##STR00022##

(33) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0037 g, 0.02 mmol), (R)-L4c (0.0569 g, 0.048 mmol), PPh.sub.3 (0.0525 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.05 g, 0.2 mmol), (±)-1o (0.2922 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2o (0.1315 g, 41%): solid; 94% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.0 min, t.sub.R(minor)=7.8 min); [α].sub.D.sup.27=+30.1 (c=1.27, CHCl.sub.3). Melting point: 89.2-90.6° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.30 (s, 4H, Ar—H), 2.31 (t, J=7.6 Hz, 2H, CH.sub.2), 2.17 (s, 3H, CH.sub.3), 1.49-1.40 (m, 2H, CH.sub.2), 1.34-1.15 (m, 10H, 5×CH.sub.2), 0.86 (t, J=7.0 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.5, 173.0, 133.6, 133.4, 128.6, 127.3, 104.4, 102.2, 31.8, 29.3, 29.2, 29.1, 28.5, 28.0, 22.6, 16.2, 14.0; IR (neat): ν=3200-2410 (br), 1938, 1675, 1415, 1274, 1091 cm.sup.−1; MS (70 eV, EI) m/z (%): 322 (M.sup.+(.sup.37C1), 1.34), 320 (M.sup.+(.sup.35C1), 3.62), 177 (100); Anal. Calcd. for C.sub.19H.sub.25ClO.sub.2: C, 71.12, H, 7.85; found C, 71.18, H, 7.87.

Example 16

(34) ##STR00023##

(35) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0037 g, 0.02 mmol), (R)-L4c (0.0566 g, 0.048 mmol), PPh.sub.3 (0.0527 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0501 g, 0.2 mmol), (±)-1p (0.2504 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=10/1) to afford a product: chiral allenic acid (S)-2p (0.0834 g, 30%): solid; 94% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=13.7 min, t.sub.R(minor)=24.1 min); [α].sub.D.sup.25=−23.3 (c=1.00, CHCl.sub.3). Melting point: 87.4-89.1° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.33-7.20 (m, 7H, Ar—H), 7.19-7.12 (m, 3H, Ar—H), 2.83 (t, J=7.6 Hz, 2H, CH.sub.3), 2.76-2.57 (m, 2H, CH.sub.2), 2.02 (s, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.9, 172.6, 141.1, 134.7, 128.5, 128.3, 127.6, 126.1, 125.9, 105.5, 100.7, 34.1, 30.3, 16.1; IR (neat): ν=3200-2410 (br), 1934, 1676, 1417, 1279, 1253, 1065 cm.sup.−1; MS (70 eV, EI) m/z (%): 279 (M.sup.++1, 1.97), 278 (M.sup.+, 9.71), 91 (100); Anal. Calcd. for C.sub.19H.sub.18O.sub.2: C, 81.99, H, 6.52; found C, 82.12, H, 6.39.

Example 17

(36) ##STR00024##

(37) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0037 g, 0.02 mmol), (R)-L4c (0.0571 g, 0.048 mmol), PPh.sub.3 (0.0525 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0375 g, 0.15 mmol), (±)-1q (0.2356 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=10/1) to afford a product: chiral allenic acid (S)-2q (0.0871 g, 33%): solid; 91% ee (HPLC conditions: AS-H column, hexane/i-PrOH=95/5, 1.3 mL/min, λ=214 nm, t.sub.R(major)=5.8 min, t.sub.R(minor)=7.4 min); [α].sub.D.sup.27=−4.1 (c=1.00, CHCl.sub.3). Melting point: 70.7-72.7° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.45-7.30 (m, 4H, Ar—H), 7.30-7.22 (m, 1H, Ar—H), 3.50 (t, J=6.6 Hz, 2H, CH.sub.2), 2.36 (t, J=7.6 Hz, 2H, CH.sub.2), 2.20 (s, 3H, CH.sub.3), 1.87-1.73 (m, 2H, CH.sub.2), 1.72-1.55 (m, 2H, CH.sub.2); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.6, 172.8, 134.7, 128.6, 127.7, 126.1, 105.7, 101.1, 44.6, 32.0, 27.8, 25.3, 16.3; IR (neat): ν=3300-2300 (br), 1933, 1672, 1418, 1272, 1101, 1059, 1015 cm.sup.−1; MS (70 eV, EI) m/z (%): 266 (M.sup.+(.sup.37C1), 2.35), 264 (M.sup.+(.sup.35C1), 7.78), 143 (100); Anal. Calcd. for C.sub.15H.sub.17ClO.sub.2: C, 68.05, H, 6.47; found C, 67.77, H, 6.59.

Example 18

(38) ##STR00025##

(39) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0037 g, 0.02 mmol), (R)-L4c (0.057 g, 0.048 mmol), PPh.sub.3 (0.0526 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0501 g, 0.2 mmol), (±)-1r (0.2166 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at −5° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=10/1) to afford a product: chiral allenic acid (S)-2r (0.0808 g, 33%): solid; 93% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=7.1 min, t.sub.R (minor)=9.0 min); [α].sub.D.sup.27=+5.5 (c=1.10, CHCl.sub.3). Melting point: 75.2-76.7° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.47-7.28 (m, 4H, Ar—H), 7.28-7.18 (m, 1H, Ar—H), 2.33 (t, J=7.8 Hz, 2H, CH.sub.3), 2.18 (s, 3H, CH.sub.3), 1.65-1.51 (m, 1H, CH), 1.43-1.29 (m, 2H, CH.sub.2), 0.87 (t, J=6.2 Hz, 6H, 2×CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.5, 173.1, 135.0, 128.5, 127.6, 126.0, 105.2, 102.0, 37.1, 27.6, 26.6, 22.44, 22.40, 16.3; IR (neat): ν=3250-2410 (br), 1936, 1674, 1467, 1418, 1279, 1256, 1066 cm.sup.−1; MS (70 eV, EI) m/z (%): 244 (M.sup.+, 2.72), 143 (100); Anal. Calcd. for C.sub.16H.sub.20O.sub.2: C, 78.65, H, 8.25; found C, 78.54, H, 8.32.

Example 19

(40) ##STR00026##

(41) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.0569 g, 0.048 mmol), PPh.sub.3 (0.0525 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.075 g, 0.3 mmol), (±)-1s (0.2133 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ethyl acetate=10/1˜5/1) to afford a product: chiral allenic acid (S)-2s (0.0702 g, 29%): solid; 93% ee (HPLC conditions: AS-H column, hexane/i-PrOH=90/10, 1.3 mL/min, λ=214 nm, t.sub.R(major)=9.9 min, t.sub.R(minor)=12.3 min); [α].sub.D.sup.25=+23.7 (c=1.10, CHCl.sub.3). Melting point: 64.4-65.6° C. (petroleum ether/ether recrystallization). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.39-7.33 (m, 4H, Ar—H), 7.33-7.27 (m, 1H, Ar—H), 2.52-2.44 (m, 2H, CH), 2.35 (t, J=7.2 Hz, 2H, CH.sub.2), 2.22 (s, 3H, CH.sub.3), 1.89 (quint, J=7.4 Hz, 2H, CH.sub.2); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.4, 171.9, 134.3, 128.7, 128.0, 126.1, 119.2, 106.3, 99.7, 27.7, 23.9, 16.5, 16.3; IR (neat): ν=3400-2650 (br), 2262, 1939, 1697, 1450, 1394, 1216, 1030 cm.sup.−1; MS (70 eV, EI) m/z (%): 242 (M.sup.++1, 3.44), 241 (M.sup.+, 19.06), 143 (100); Anal. Calcd. for C.sub.15H.sub.15NO.sub.2: C, 74.67, H, 6.27; found C, 74.43, H, 6.33.

Example 20

(42) ##STR00027##

(43) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.0571 g, 0.048 mmol), PPh.sub.3 (0.0526 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0502 g, 0.2 mmol), (±)-1t (0.1867 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2t (0.0668 g, 31%): solid; 90% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=10.4 min, t.sub.R(minor)=12.6 min); [α].sub.D.sup.26=−2.2 (c=1.00, CHCl.sub.3). Melting point: 94.6-96.1° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.41-7.30 (m, 4H, Ar—H), 7.29-7.22 (m, 1H, Ar—H), 5.97-5.74 (m, 1H, ═CH), 5.13 (d, J=16.8 Hz, 1H, one proton of ═CH.sub.2), 5.03 (d, J=10.0 Hz, 1H, one proton of ═CH.sub.2), 3.08 (d, J=6.8 Hz, 2H, CH.sub.2), 2.19 (s, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.9, 172.1, 134.8, 134.7, 128.6, 127.7, 126.1, 116.5, 105.8, 100.2, 33.1, 16.3; IR (neat): ν=3200-2410 (br), 1933, 1677, 1414, 1263, 1065 cm.sup.−1; MS (70 eV, EI) m/z (%): 215 (M.sup.++1, 5.09), 214 (M.sup.+, 16.32), 171 (100); HRMS calcd for C.sub.14H.sub.14O.sub.2 [M.sup.+]: 214.0994, found: 214.0995.

Example 21

(44) ##STR00028##

(45) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.057 g, 0.048 mmol), PPh.sub.3 (0.0524 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0501 g, 0.2 mmol), (±)-1u (0.2672 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2u (0.0947 g, 32%): solid; >99% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 0.8 mL/min, λ=214 nm, t.sub.R(major)=13.6 min); [α].sub.D.sup.26=+84.6 (c=1.32, CHCl.sub.3). Melting point: 119.2-120.9° C. (petroleum ether/dichloromethane). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.46 (d, J=8.8 Hz, 2H, Ar—H), 7.25 (d, J=8.4 Hz, 2H, Ar—H), 2.80 (heptet, J=6.8 Hz, 1H, CH), 2.18 (s, 3H, CH.sub.3), 1.09 (d, J=6.8 Hz, 6H, 2×CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=211.3, 172.4, 134.0, 131.7, 127.4, 121.5, 109.0, 105.8, 28.2, 22.1, 22.1, 16.2; IR (neat): ν=3200-2410 (br), 1938, 1673, 1484, 1412, 1271, 1074 cm.sup.−1; MS (70 eV, EI) m/z (%): 296 (M.sup.+(.sup.81Br), 63.64), 294 (M.sup.+(.sup.79Br), 63.57), 155 (100); HRMS calcd for C.sub.14H.sub.15.sup.79BrO.sub.2 [M.sup.+]: 294.0255, found: 294.0256.

Example 22

(46) ##STR00029##

(47) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.057 g, 0.048 mmol), PPh.sub.3 (0.0526 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.05 g, 0.2 mmol), (±)-1v (0.2165 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2v (0.1004 g, 41%): oil substance; 94% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.3 min, t.sub.R(minor)=8.8 min); [α].sub.D.sup.28=+103.4 (c=1.10, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.29-7.08 (m, 4H, Ar—H), 2.50-2.32 (m, 5H, CH.sub.2 and CH.sub.3), 2.32-2.12 (m, 2H, CH.sub.2), 1.60-1.42 (m, 2H, CH.sub.2), 1.11 (t, J=7.4 Hz, 3H, CH.sub.3), 0.93 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=209.2, 174.1, 136.02, 135.97, 130.4, 128.4, 127.5, 125.8, 111.2, 100.6, 30.5, 27.1, 21.4, 20.0, 13.8, 12.2; IR (neat): ν=3200-2410 (br), 1948, 1674, 1414, 1270, 1130 cm.sup.−1; MS (70 eV, EI) m/z (%): 245 (M.sup.++1, 12.45), 244 (M.sup.+, 69.97), 229 (100); HRMS calcd for C.sub.16H.sub.20O.sub.2 [M.sup.+]: 244.1458, found: 244.1455.

Example 23

(48) ##STR00030##

(49) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0037 g, 0.02 mmol), (R)-L4c (0.0571 g, 0.048 mmol), PPh.sub.3 (0.0525 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.05 g, 0.2 mmol), (±)-1w (0.229 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2w (0.0723 g, 28%): oil substance; 92% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=5.6 min, t.sub.R(minor)=7.7 min); [α].sub.D.sup.27=+86.2 (c=1.10, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.26-7.20 (m, 1H, Ar—H), 7.20-7.11 (m, 3H, Ar—H), 2.50-2.15 (m, 7H, 2×CH.sub.2 and CH.sub.3), 1.54-1.40 (m, 2H, CH.sub.2), 1.40-1.28 (m, 2H, CH.sub.2), 1.12 (t, J=7.4 Hz, 3H, CH.sub.3), 0.90 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=209.1, 174.1, 136.01, 135.96, 130.4, 128.4, 127.5, 125.8, 111.2, 100.7, 30.3, 28.0, 27.1, 22.3, 20.0, 13.8, 12.2; IR (neat): ν=3200-2400 (br), 1949, 1675, 1414, 1275, 1086 cm.sup.−1; MS (70 eV, EI) m/z (%): 259 (M.sup.++1, 6.05), 258 (M.sup.+, 32.38), 129 (100); HRMS calcd for C.sub.17H.sub.22O.sub.2 [M.sup.+]: 258.1620, found: 258.1623.

Example 24

(50) ##STR00031##

(51) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0036 g, 0.02 mmol), (R)-L4c (0.057 g, 0.048 mmol), PPh.sub.3 (0.0527 g, 0.2 mmol), (PhO).sub.2PO.sub.2H (0.0501 g, 0.2 mmol), (±)-1x (0.2287 g, 1 mmol), water (360 μL, d=1.0 g/mL, 0.36 g, 20 mmol), toluene (5 mL), reacted at −5° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2x (0.0928 g, 36%): solid; 90% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=9.2 min, t.sub.R(minor)=11.2 min). Melting point: 107.7-108.6° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.39-7.29 (m, 1H, Ar—H), 7.17-7.05 (m, 3H, Ar—H), 2.82 (t, J=6.2 Hz, 2H, CH.sub.2), 2.72-2.56 (m, 2H, CH.sub.2), 2.33 (t, J=7.4 Hz, 2H, CH.sub.2), 2.20-1.83 (m, 2H, CH.sub.2), 1.52-1.41 (m, 2H, CH.sub.2), 1.41-1.28 (m, 2H, CH.sub.2), 0.88 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=210.5, 173.0, 136.8, 129.4, 129.3, 127.5, 127.3, 126.2, 106.2, 102.8, 30.2, 29.8, 28.4, 28.0, 22.7, 22.3, 13.8; IR (neat): ν=3200-2400, 1931, 1670, 1418, 1279 cm.sup.−1; MS (70 eV, EI) m/z (%): 257 (M.sup.++1, 1.91), 256 (M.sup.+, 8.77), 169 (100); Anal. Calcd. for C.sub.17H.sub.20O.sub.2: C, 79.65, H, 7.86; found C, 79.16, H, 7.83.

Example 25

(52) ##STR00032##

(53) PdCl.sub.2 (0.0356 g, 0.2 mmol), chiral diphosphine ligand (R)-L4c (0.5776 g, 0.48 mmol), monophosphine ligand PPh.sub.3 (0.5242 g, 2 mmol), and (PhO).sub.2PO.sub.2H (0.5006 g, 2 mmol) were added to a dried Schlenk reaction tube. The reaction tube was then plugged with a rubber stopper, and then connected with the vacuum pump, and replaced the argon three times under the argon atmosphere. And under the protection of the argon, tertiary propargyl alcohol (±)-1a (2.0240 g, 10 mmol), toluene (30 mL), water (3.6041 g, 200 mmol) and toluene (20 ml) were added. After closed the argon, freezed the reaction tube in a liquid nitrogen bath for 15 minutes, inserted carbon monoxide balloon (about 2 liters), replaced carbon monoxide under the atmosphere of carbon monoxide three times, then removed the liquid nitrogen bath. When the reaction system returns to room temperature and melted into liquid, put the reaction tube in the preset 0° C. low-temperature bath and stirred for 18 hours. The reaction tube was taken out of the low-temperature bath, and returned to the room temperature and added H.sub.2O.sub.2 (400 μL, d=1.13 g/mL, 30 wt. % in H.sub.2O, 0.135 g, 4 mmol), stirred at the room temperature for 30 minutes. The reaction solution was diluted with ethyl acetate (50 mL), the mixture solution is filtered with silica gel short column (3 cm), and then washed with ethyl acetate (100 mL), concentrated, and subjected to the flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.8259 g, 37%) and (S)-1a (1.0516 g, 52%).

(54) (S)-2a: 93% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=8.5 min, t.sub.R(minor)=10.7 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.45-7.29 (m, 4H, Ar—H), 7.29-7.17 (m, 1H, Ar—H), 2.32 (t, J=7.4 Hz, 2H, CH.sub.2), 2.19 (s, 3H, CH.sub.3), 1.54-1.40 (m, 2H, CH.sub.2), 1.40-1.27 (m, 2H, CH.sub.2), 0.88 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.5, 172.8, 135.0, 128.5, 127.5, 126.1, 105.2, 101.8, 30.2, 28.3, 22.3, 16.3, 13.8.

(55) (S)-1a: 63% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(minor)=7.2 min, t.sub.R(major)=11.9 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.64 (d, J=7.2 Hz, 2H, Ar—H), 7.32 (t, J=7.6 Hz, 2H, Ar—H), 7.28-7.20 (m, 1H, Ar—H), 2.64 (s, 1H, OH), 2.25 (t, J=7.0 Hz, 2H, CH.sub.2), 1.72 (s, 3H, CH.sub.3), 1.58-1.48 (m, 2H, CH.sub.2), 1.48-1.34 (m, 2H, CH.sub.2), 0.91 (t, J=7.2 Hz, 3H, CH.sub.3).

(56) Operations were conducted by referring to Example 25. PdCl.sub.2 (0.0177 g, 0.1 mmol), (R)-L4c (0.2896 g, 0.24 mmol), PPh.sub.3 (0.2624 g, 1 mmol), (PhO).sub.2PO.sub.2H (0.2501 g, 1 mmol), (5)-1a (1.0109 g, 5 mmol), water (1.8052 g, 100 mmol), toluene (25 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (R)-2a (0.8172 g, 71%): solid; 98% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(minor)=8.1 min, t.sub.R(major)=9.8 min); [α].sub.D.sup.28=−26.2 (c=0.90, CHCl.sub.3). Melting point: 92.2-93.3° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.44-7.29 (m, 4H, Ar—H), 7.29-7.20 (m, 1H, Ar—H), 2.32 (t, J=7.6 Hz, 2H, CH.sub.2), 2.19 (s, 3H, CH.sub.3), 1.54-1.41 (m, 2H, CH.sub.2), 1.41-1.26 (m, 2H, CH.sub.2), 0.88 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.5, 172.8, 135.0, 128.5, 127.6, 126.1, 105.2, 101.8, 30.2, 28.3, 22.3, 16.3, 13.8; IR (neat): ν=3200-2410 (br), 1936, 1678, 1446, 1280, 1066 cm.sup.−1; MS (70 eV, EI) m/z (%): 230 (M.sup.+, 2.74), 143 (100); HRMS calcd for C.sub.15H.sub.18O.sub.2 [M.sup.+]: 230.1301, found: 230.1295.

Example 26

(57) ##STR00033##

(58) Operations were conducted by referring to Example 25. PdCl.sub.2 (0.0358 g, 0.2 mmol), (R)-L4c (0.5779 g, 0.48 mmol), PPh.sub.3 (0.5253 g, 2 mmol), (PhO).sub.2PO.sub.2H (0.5005 g, 2 mmol), (±)-1f (2.3685 g, 10 mmol), water (3.6031 g, 200 mmol), toluene (50 mL), reacted at 0° C. for 24 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=5/1) to afford products: chiral allenic acid (S)-2f (1.0946 g, 41%) and (S)-1f (1.2385 g, 52%).

(59) (S)-2f: 95% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=8.6 min, t.sub.R(minor)=9.6 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.29 (s, 4H, Ar—H), 2.32 (t, J=7.6 Hz, 2H, CH.sub.2), 2.16 (s, 3H, CH.sub.3), 1.50-1.40 (m, 2H, CH.sub.2), 1.40-1.28 (m, 2H, CH.sub.2), 0.87 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.5, 172.9, 133.6, 133.4, 128.7, 127.3, 104.4, 102.2, 30.2, 28.2, 22.2, 16.3, 13.8.

(60) (S)-1f: 75% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (minor)=7.3 min, t.sub.R(major)=10.1 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.58 (d, J=8.4 Hz, 2H, Ar—H), 7.31 (d, J=8.4 Hz, 2H, Ar—H), 2.33-2.20 (m, 3H, CH.sub.2 and OH), 1.71 (s, 3H, CH.sub.3), 1.57-1.48 (m, 2H, CH.sub.2), 1.48-1.36 (m, 2H, CH.sub.2), 0.93 (t, J=7.4 Hz, 3H, CH.sub.3).

(61) Operations were conducted by referring to Example 25. PdCl.sub.2 (0.0185 g, 0.1046 mmol), (S)-L4c (0.3025 g, 0.251 mmol), PPh.sub.3 (0.2748 g, 1.046 mmol), (PhO).sub.2PO.sub.2H (0.2621 g, 1.046 mmol), (5)-1f (1.2385 g, 5.23 mmol), water (1.8883 g, 104.6 mmol), toluene (25 mL), reacted at 0° C. for 24 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=5/1) to afford a product: chiral allenic acid (R)-2f (0.9115 g, 66%): solid; 98% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(minor)=8.9 min, t.sub.R(major)=9.8 min); [α].sub.D.sup.26=−39.7 (c=1.00, CHCl.sub.3). Melting point: 108.6-110.0° C. (measuring directly after solvent evaporates to dryness). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.31 (s, 4H, Ar—H), 2.33 (t, J=7.6 Hz, 2H, CH.sub.2), 2.17 (s, 3H, CH.sub.3), 1.50-1.40 (m, 2H, CH.sub.2), 1.40-1.29 (m, 2H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.5, 172.9, 133.6, 133.4, 128.7, 127.3, 104.4, 102.2, 30.1, 28.2, 22.2, 16.2, 13.8; IR (neat): ν=3200-2410 (br), 1940, 1680, 1416, 1280, 1090 cm.sup.−1; MS (70 eV, EI) m/z (%): 266 (M.sup.+(.sup.37C1), 1.42), 264 (M.sup.+(.sup.35C1), 3.93), 177 (100); HRMS calcd for C.sub.15H.sub.17.sup.35ClO.sub.2 [M.sup.+]: 264.0912, found: 264.0913.

Example 27

(62) ##STR00034##

(63) Operations were conducted by referring to Example 25. PdCl.sub.2 (0.0357 g, 0.2 mmol), (R)-L4c (0.5774 g, 0.48 mmol), PPh.sub.3 (0.524 g, 2 mmol), (PhO).sub.2PO.sub.2H (0.7505 g, 3 mmol), (±)-1k (1.8235 g, 10 mmol), water (3.6009 g, 200 mmol), toluene (50 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford products: chiral allenic acid (S)-2k (0.9668 g, 46%) and (S)-1k (0.7841 g, 43%).

(64) (S)-2k: Melting point: 42.0-44.3° C. (petroleum ether/dichloromethane recrystallization); >99% ee (HPLC conditions: AD-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=7.4 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=2.27-2.10 (m, 2H, CH.sub.2), 1.77 (s, 3H, CH.sub.3), 1.47-1.28 (m, 4H, 2×CH.sub.2), 1.10 (s, 9H, 3×CH.sub.3), 0.90 (t, J=7.0 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=208.2, 174.5, 112.8, 99.4, 34.2, 30.3, 28.8, 28.0, 22.3, 14.0, 13.9.

(65) (S)-1k: >99% ee (HPLC conditions: IC column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=4.7 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=2.20 (t, J=6.8 Hz, 2H, CH.sub.2), 1.78 (s, 1H, OH), 1.55-1.34 (m, 7H, 2×CH.sub.2 and CH.sub.3), 1.03 (s, 9H, 3×CH.sub.3), 0.91 (t, J=7.2 Hz, 3H, CH.sub.3).

(66) Operations were conducted by referring to Example 25. PdCl.sub.2 (0.0152 g, 0.086 mmol), (S)-L4c (0.2489 g, 0.2064 mmol), PPh.sub.3 (0.2253 g, 0.86 mmol), (PhO).sub.2PO.sub.2H (0.3226 g, 1.29 mmol), (S)-1k (0.7841 g, 4.3 mmol), water (1.5471 g, 86 mmol), toluene (21 mL), reacted at 0° C. for 24 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (R)-2k (0.7248 g, 80%): solid; >99% ee (HPLC conditions: AD-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=6.7 min); [α].sub.D.sup.27=−37.4 (c=1.00, CHCl.sub.3). Melting point: 42.5-44.2° C. (petroleum ether/dichloromethane recrystallization). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=2.26-2.10 (m, 2H, CH.sub.2), 1.77 (s, 3H, CH.sub.3), 1.48-1.28 (m, 4H, 2×CH.sub.2), 1.10 (s, 9H, 3×CH.sub.3), 0.91 (t, J=7.0 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=208.1, 174.5, 112.8, 99.4, 34.2, 30.3, 28.8, 28.0, 22.3, 14.0, 13.9; IR (neat): ν=3210-2410 (br), 1947, 1669, 1413, 1276, 1241, 1113 cm.sup.−1; MS (ESI) m/z: 211 (M.sup.+H+); HRMS calcd for C.sub.13H.sub.23O.sub.2 [M+H.sup.+]: 211.1693, found: 211.1697.

Example 28

(67) ##STR00035##

(68) Operations were conducted by referring to Example 25. PdCl.sub.2 (0.03576 g, 0.2 mmol), (R)-L4c (0.5779 g, 0.48 mmol), PPh.sub.3 (0.5247 g, 2 mmol), (PhO).sub.2PO.sub.2H (0.5006 g, 2 mmol), (±)-1v (2.1625 g, 10 mmol), water (3.6017 g, 200 mmol), toluene (50 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford products: chiral allenic acid (S)-2v (0.9553 g, 39%) and (S)-1v (1.1165 g, 52%).

(69) (S)-2v: 93% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.6 min, t.sub.R(minor)=9.2 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.27-7.20 (m, 1H, Ar—H), 7.20-7.11 (m, 3H, Ar—H), 2.47-2.32 (m, 5H, CH.sub.2 and CH.sub.3), 2.32-2.12 (m, 2H, CH.sub.2), 1.58-1.44 (m, 2H, CH.sub.2), 1.11 (t, J=7.4 Hz, 3H, CH.sub.3), 0.93 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=209.2, 174.1, 136.02, 135.97, 130.4, 128.4, 127.5, 125.8, 111.2, 100.6, 30.5, 27.1, 21.4, 20.0, 13.8, 12.2.

(70) (S)-1v (1.1165 g, 52%): 63% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(minor)=5.6 min, t.sub.R(major)=7.1 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.77-7.68 (m, 1H, Ar—H), 7.23-7.10 (m, 3H, Ar—H), 2.58 (s, 3H, CH.sub.3), 2.25 (t, J=7.0 Hz, 2H, CH.sub.2), 2.21 (s, 1H, OH), 2.09-1.90 (m, 2H, CH.sub.2), 1.60-1.51 (m, 2H, CH.sub.2), 1.08-0.91 (m, 6H, 2×CH.sub.3).

(71) Operations were conducted by referring to Example 25. PdCl.sub.2 (0.0181 g, 0.1032 mmol), (S)-L4c (0.2981 g, 0.248 mmol), PPh.sub.3 (0.2704 g, 1.032 mmol), (PhO).sub.2PO.sub.2H (0.2581 g, 1.032 mmol), (S)-1v (1.1165 g, 5.16 mmol), water (1.8582 g, 103.2 mmol), toluene (25.8 mL), reacted at 0° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (R)-2v (0.8785 g, 70%): oil substance: 99% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(minor)=5.6 min, t.sub.R(major)=6.7 min); [α].sub.D.sup.28=−107.5 (c=1.00, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.30-7.08 (m, 4H, Ar—H), 2.48-2.32 (m, 5H, CH.sub.2 and CH.sub.3), 2.32-2.10 (m, 2H, CH.sub.2), 1.61-1.49 (m, 2H, CH.sub.2), 1.11 (t, J=7.2 Hz, 3H, CH.sub.3), 0.93 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=209.1, 174.1, 136.01, 135.97, 130.4, 128.4, 127.5, 125.8, 111.2, 100.6, 30.5, 27.1, 21.4, 20.0, 13.8, 12.2; IR (neat): ν=3200-2410 (br), 1949, 1675, 1414, 1268, 1121 cm.sup.−1; MS (70 eV, EI) m/z (%): 245 (M.sup.++1, 9.12), 244 (M.sup.+, 45.59), 129 (100); HRMS calcd for C.sub.16H.sub.20O.sub.2 [M.sup.+]: 244.1458, found: 244.1454.

Example 29

(72) ##STR00036##

(73) Operations were conducted by referring to Example 25. PdCl.sub.2 (0.1779 g, 1.0 mmol), (R)-L4c (2.8891 g, 2.4 mmol), PPh.sub.3 (2.6243 g, 10 mmol), (PhO).sub.2PO.sub.2H (2.5036 g, 10 mmol), (±)-1a (10.1061 g, 50 mmol), water (18.0050 g, 1000 mmol), toluene (250 mL), reacted at 0° C. for 24 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=5/1) to afford products: chiral allenic acid (S)-2a (5.1316 g, 45%) and (5)-1a (5.1163 g, 51%).

(74) (S)-2a: 93% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=7.9 min, t.sub.R(minor)=9.7 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.45-7.28 (m, 4H, Ar—H), 7.27-7.18 (m, 1H, Ar—H), 2.33 (t, J=7.4 Hz, 2H, CH.sub.2), 2.18 (s, 3H, CH.sub.3), 1.55-1.40 (m, 2H, CH.sub.2), 1.40-1.27 (m, 2H, CH.sub.2), 0.87 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.6, 173.1, 135.0, 128.5, 127.5, 126.1, 105.2, 101.8, 30.2, 28.3, 22.2, 16.3, 13.8.

(75) (S)-1a: 69% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (minor)=7.1 min, t.sub.R (major)=11.2 min). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.65 (d, J=7.2 Hz, 2H, Ar—H), 7.35 (t, J=7.4 Hz, 2H, Ar—H), 7.31-7.23 (m, 1H, Ar—H), 2.36 (s, 1H, OH), 2.28 (t, J=7.0 Hz, 2H, CH.sub.2), 1.74 (s, 3H, CH.sub.3), 1.58-1.49 (m, 2H, CH.sub.2), 1.49-1.35 (m, 2H, CH.sub.2), 0.93 (t, J=7.2 Hz, 3H, CH.sub.3).

(76) Operations were conducted by referring to Example 25. PdCl.sub.2 (0.09 g, 0.5063 mmol), (5)-L4c (1.4634 g, 1.2151 mmol), PPh.sub.3 (1.3287 g, 5.0631 mmol), (PhO).sub.2PO.sub.2H (1.268 g, 5.0631 mmol), (5)-1a (5.1163 g, 25.31 mmol), water (9.1162 g, 506.31 mmol), toluene (127 mL), reacted at 0° C. for 20 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (R)-2a (4.3055 g, 74%): solid; 96% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(minor)=8.4 min, t.sub.R(major)=10.4 min); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.43-7.29 (m, 4H, Ar—H), 7.29-7.21 (m, 1H, Ar—H), 2.33 (t, J=7.6 Hz, 2H, CH.sub.2), 2.19 (s, 3H, CH.sub.3), 1.54-1.41 (m, 2H, CH.sub.2), 1.41-1.28 (m, 2H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=212.6, 173.1, 135.0, 128.5, 127.5, 126.0, 105.2, 101.8, 30.2, 28.3, 22.2, 16.3, 13.8.

Example 30

(77) ##STR00037##

(78) (R)-2a (0.1153 g, 0.5 mmol, 98% ee) was added to a dried Schlenk reaction tube, and then took the reaction tube into the glove box and weighed CuCl (0.0023 g, 0.02 mmol), and then took the tube out of the glove box, and added methanol (5 mL) under the protection of argon. The reaction was complete after being stirred at 60° C. oil bath, for 10 h as monitored by thin layer chromatography (TLC). After the methanol was dried, ethyl acetate (5 mL) was added to dissolve the product, quickly filtered by silica gel short column (3 cm) and eluted with ethyl acetate (15 mL), concentrated, and subjected to the flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=50/1/1) to afford a cyclic product (S)-3 (0.1097 g, 95%): oil substance; 98% ee (HPLC conditions: AD-H column, hexane/i-PrOH=100/1, 0.9 mL/min, λ=214 nm, t.sub.R(minor)=26.8 min, t.sub.R(major)=29.9 min); [α].sub.D.sup.27=−167.8 (c=1.15, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.44-7.26 (m, 5H, Ar—H), 7.23 (s, 1H, ═CH), 2.35-2.19 (m, 2H, CH.sub.2), 1.78 (s, 3H, CH.sub.3), 1.60-1.47 (m, 2H, CH.sub.2), 1.43-1.27 (m, 2H, CH.sub.2), 0.92 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=173.1, 152.2, 140.1, 132.2, 128.6, 127.9, 124.6, 86.5, 29.3, 26.7, 24.6, 22.1, 13.6; IR (neat): ν=2957, 2929, 2865, 1751, 1448, 1258, 1039 cm.sup.−1; MS (70 eV, EI) m/z (%): 231 (M.sup.++1, 1.77), 230 (M.sup.+, 11.21), 187 (100); HRMS calcd for C.sub.15H.sub.18O.sub.2 [M.sup.+]: 230.1307, found: 230.1304.

Example 31

(79) ##STR00038##

(80) (R)-2a (0.1151 g, 0.5 mmol, 98% ee), NBS (0.1075 g, 0.6 mmol), chloroform (5 mL) were added to a dried Schlenk reaction tube, and placing the reaction tube at the room temperature. The reaction was complete after being stirred for 2 h as monitored by thin layer chromatography (TLC). After the methanol was dried, subjected to the flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=50/1/1) to afford a cyclic product (R)-4 (0.1484 g, 96%): solid; 98% ee (HPLC conditions: AD-H column, hexane/i-PrOH=100/1, 0.7 mL/min, λ=214 nm, t.sub.R (minor)=11.6 min, t.sub.R (major)=12.9 min); [α].sub.D.sup.27=−149.4 (c=1.30, CHCl.sub.3). Melting point: 49.4-49.9° C. (petroleum ether/dichloromethane). .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.44-7.29 (m, 5H, Ar—H), 2.36 (t, J=7.6 Hz, 2H, CH.sub.2), 1.91 (s, 3H, CH.sub.3), 1.65-1.50 (m, 2H, CH.sub.2), 1.44-1.26 (m, 2H, CH.sub.2), 0.93 (t, J=7.4 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=170.4, 150.4, 137.2, 131.2, 128.8, 128.6, 125.5, 88.1, 29.0, 24.8, 23.8, 22.3, 13.7; IR (neat): ν=2957, 2930, 2862, 1757, 1650, 1448, 1247, 1042 cm.sup.−1; MS (ESI) m/z (%): 311 (M(.sup.81Br)+H.sup.+), 309 (M(.sup.79Br)+H.sup.+); Anal. Calcd. for C.sub.15H.sub.17BrO.sub.2: C, 58.27, H, 5.54; found: C, 58.18, H, 5.56.

Example 32

(81) ##STR00039##

(82) (R)-2a (0.1152 g, 0.5 mmol, 98% ee), PdCl.sub.2 (0.0044 g, 0.025 mmol), allyl bromide (260 uL, d=1.398 g/mL, 0.3635 g, 3.0 mmol) were added to a dried Schlenk reaction tube, and then added DMA (N,N-dimethylacetamide) (5 mL) in the protection of argon. The reaction was complete after being stirred at 50° C. oil bath, for 20 h as monitored by thin layer chromatography (TLC). Then the reaction was quenched by water (5 mL), and the aqueous layer was extracted with ether (5 mL×3). The combined organic layer was separated and dried over anhydrous sodium sulfate, then filtered, concentrated, and subjected to the flash silica gel column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=50/1/1) to afford a cyclic product (R)-5 (0.1127 g, 83%): oil substance; 97% ee (HPLC conditions: IF column, hexane/i-PrOH=95/5, 1.0 mL/min, λ=214 nm, t.sub.R(major)=14.0 min, t.sub.R(minor)=15.7 min); [α].sub.D.sup.27=−193.6 (c=1.27, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.45-7.23 (m, 5H, Ar—H), 5.58-5.38 (m, 1H, ═CH), 5.02 (d, J=4.4 Hz, 1H, one proton of ═CH.sub.2), 4.98 (s, 1H, one proton of ═CH.sub.2), 2.99 (dd, J.sub.1=15.6 Hz, J.sub.2=6.0 Hz, 1H, one proton of CH.sub.2), 2.86 (dd, J.sub.1=15.6 Hz, J.sub.2=7.2 Hz, 1H, one proton of CH.sub.2), 2.30 (t, J=7.8 Hz, 2H, CH.sub.2), 1.84 (s, 3H, CH.sub.3), 1.60-1.48 (m, 2H, CH.sub.2), 1.43-1.28 (m, 2H, CH.sub.2), 0.93 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=173.8, 164.2, 138.3, 132.3, 128.5, 128.3, 127.5, 125.4, 117.5, 87.8, 30.6, 30.0, 23.4, 23.2, 22.6, 13.7; IR (neat): ν=2954, 2930, 2865, 1748, 1448, 1257, 1207, 1038 cm.sup.−1; MS (70 eV, EI) m/z (%): 271 (M.sup.++1, 3.32), 270 (M.sup.+, 16.82), 229 (100); HRMS calcd for C.sub.18H.sub.22O.sub.2 [M.sup.+]: 270.1620, found: 270.1622.

Example 33

(83) ##STR00040##

(84) (R)-2a (0.1152 g, 0.5 mmol, 98% ee) and PdCl.sub.2 (0.0045 g, 0.025 mmol) were added to a dried Schlenk reaction tube, and then replaced argon three times and added allenic alcohol (0.0875 g, 1.25 mmol), TFA (trifluoroacetic acid) (30 uL, d=1.535 g/mL, 0.0456 g, 0.4 mmol) and DMA (N,N-dimethylacetamide) (5 mL). The reaction was complete after being stirred at 30° C. oil bath, for 8 h as monitored by thin layer chromatography (TLC). Then the reaction was quenched by water (5 mL), and the aqueous layer was extracted with ether (5 mL×3). The combined organic layer was washed with brine and dried over anhydrous sodium sulfate, then filtered, concentrated, and subjected to the flash silica gel column chromatography (eluent: petroleum ether (60˜90° C.)/ethyl acetate=50/1) to afford a cyclic product (R)-6 (0.1113 g, 79%): oil substance; 97% ee (HPLC conditions: AD-H column, hexane/i-PrOH=95/5, 1.0 mL/min, λ=214 nm, t.sub.R(minor)=6.8 min, t.sub.R(major)=7.4 min); [α].sub.D.sup.28=−176.7 (c=1.0, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.40-7.17 (m, 5H, Ar—H), 6.28 (dd, J.sub.1=17.4 Hz, J.sub.2=10.6 Hz, 1H, ═CH), 5.27 (s, 1H, one proton of ═CH.sub.2), 5.00 (d, J=10.4 Hz, 1H, ═CH.sub.2), 4.74 (d, J=17.6 Hz, 1H, ═CH.sub.2), 4.47 (s, 1H, one proton of ═CH.sub.2), 2.26-2.07 (m, 2H, CH.sub.2), 1.84 (s, 3H, CH.sub.3), 1.58-1.42 (m, 2H, CH.sub.2), 1.35-1.21 (m, 2H, CH.sub.2), 0.87 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=173.3, 163.3, 138.7, 138.3, 135.8, 128.6, 128.3, 128.1, 125.4, 120.1, 117.2, 88.0, 29.7, 24.3, 24.0, 22.5, 13.7; IR (neat): ν=2955, 2865, 1753, 1450, 1221, 1040 cm.sup.−1; MS (70 eV, EI) m/z (%): 283 (M.sup.++1, 1.95), 282 (M.sup.+, 9.60), 91 (100); HRMS calcd for C.sub.19H.sub.22O.sub.2 [M.sup.+]: 282.1614, found: 282.1614.

Example 34

(85) ##STR00041##

(86) (R)-2a (0.1151 g, 0.5 mmol, 98% ee), K.sub.2CO.sub.3 (0.1034 g, 0.75 mmol), DMF (N,N-dimethylformamide) (2.5 mL) were added to a dried Schlenk reaction tube, and putting the reaction tube into −5° C. cold bath and added CH.sub.3I (methyl iodide) (47 μL, d=2.28 g/mL, 0.1061 g, 0.75 mmol). The reaction was complete after being stirred at a −5° C. cold bath, for 1.5 h as monitored by thin layer chromatography (TLC). Then the reaction was quenched by water (10 mL), and the aqueous layer was extracted with ether (10 mL×3). The combined organic phases were washed with saturated ammonium chloride solution (10 mL) and brine and dried over anhydrous sodium sulfate, then filtered, concentrated, and subjected to the flash silica gel column chromatography (eluent: petroleum ether (60˜90° C.)/ethyl acetate=20/1) to afford oily chiral allenic acid ester S1, and the S1 was directly used in the next reaction.

(87) S1 and toluene (5 mL) were added to a dried Schlenk reaction tube, and putting the reaction tube into −78° C. and added DIBAL-H (diisobutyl-aluminum hydride) (1.05 mL, 1.0 M in Hexane, 1.05 mmol) drop wise. The reaction was complete after being stirred at −78° C., for 4 h as monitored by thin layer chromatography (TLC). Then the reaction was quenched by methanol (5 mL) at −78° C., and took the reaction tube out of cold bath, returned to the room temperature, and added water (10 mL) and 1 mol/L aqueous hydrochloric acid solution (10 mL), and the aqueous layer was extracted with ether (10 mL×3). The combined organic layer was washed with brine (10 mL) once, separated and dried over anhydrous sodium sulfate, then filtered, concentrated, and subjected to the flash silica gel column chromatography (eluent: petroleum ether (60˜90° C.)/ethyl acetate=20/1) to afford allenic alcohol (R)-7 (0.0834 g, 77%): oil substance; 97% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (minor)=8.5 min, t.sub.R(major)=11.2 min); [α].sub.D.sup.23=+62.0 (c=1.01, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): δ=7.40 (d, J=7.6 Hz, 2H, Ar—H), 7.31 (t, J=7.6 Hz, 2H, Ar—H), 7.20 (t, J=7.2 Hz, 1H, Ar—H), 4.27-3.99 (m, 2H), 2.22-2.02 (m, 5H, CH.sub.2 and CH.sub.3), 1.59 (s, 1H, OH), 1.53-1.42 (m, 2H, CH.sub.2), 1.42-1.28 (m, 2H, CH.sub.2), 0.89 (t, J=7.2 Hz, 3H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): δ=199.0, 137.5, 128.3, 126.7, 125.6, 108.0, 104.8, 63.2, 29.9, 29.4, 22.5, 17.4, 13.9; IR (neat): ν=3315, 2954, 2925, 2858, 1948, 1597, 1462, 1067, 1024 cm.sup.−′; MS (70 eV, EI) m/z (%): 216 (M.sup.+, 1.40), 143 (100); HRMS calcd for C.sub.15H.sub.20O [M.sup.+]: 216.1509, found: 216.1512.

Example 35

(88) ##STR00042##

(89) Operations were conducted by referring to Example 1. [PdCl(π-allyl)].sub.2 (0.0015 g, 0.004 mmol), (R)-L4c (0.0148 g, 0.012 mmol), PPh.sub.3 (0.0105 g, 0.04 mmol), (PhO).sub.2PO.sub.2H (0.001 g, 0.004 mmol), (±)-1a (0.0432 g, 1 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0167 g, 44%): oil substance; 85% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=6.4 min, t.sub.R (minor)=9.4 min).

Example 36

(90) ##STR00043##

(91) Operations were conducted by referring to Example 1. Pd(PPh.sub.3).sub.4 (0.0045 g, 0.004 mmol), (R)-L4c (0.0143 g, 0.012 mmol), (PhO).sub.2PO.sub.2H (0.0011 g, 0.004 mmol), (±)-1a (0.0406 g, 0.2 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0203 g, 44%): oil substance; 63% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.4 min, t.sub.R(minor)=9.3 min).

Example 37

(92) ##STR00044##

(93) Operations were conducted by referring to Example 1. Pd.sub.2(dba).sub.3.CHCl.sub.3 (0.0045 g, 0.004 mmol), (R)-L4c (0.0143g, 0.012 mmol), PPh.sub.3 (0.0108g, 0.04 mmol), (PhO).sub.2PO.sub.2H (0.0012 g, 0.004 mmol), (±)-1a (0.0412 g, 0.2 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0188 g, 40%): oil substance; 86% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.6 min, t.sub.R(minor)=9.4 min).

Example 38

(94) ##STR00045##

(95) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0015 g, 0.004 mmol), (R)-L4c (0.0146 g, 0.012 mmol), P(2-furyl).sub.3 (0.0096 g, 0.04 mmol), (PhO).sub.2PO.sub.2H (0.001 g, 0.004 mmol), (±)-1a (0.0409 g, 1 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0256 g, 55%): oil substance; 65% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.5 min, t.sub.R(minor)=9.7 min).

Example 39

(96) ##STR00046##

(97) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0016 g, 0.004 mmol), (R)-L4c (0.0143 g, 0.012 mmol), P(2-MeC.sub.6H.sub.4).sub.3 (0.0122 g, 0.04 mmol), (PhO).sub.2PO.sub.2H (0.0011 g, 0.004 mmol), (±)-1a (0.0411 g, 1 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0286 g, 61%): oil substance; 40% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.5 min, t.sub.R(minor)=9.7 min).

Example 40

(98) ##STR00047##

(99) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0015 g, 0.004 mmol), (R)-L4c (0.0148 g, 0.012 mmol), P(3-MeC.sub.6H.sub.4).sub.3 (0.0129 g, 0.04 mmol), (PhO).sub.2PO.sub.2H (0.0011 g, 0.004 mmol), (±)-1a (0.0422 g, 1 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0226 g, 47%): oil substance; 66% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=6.4 min, t.sub.R (minor)=9.5 min).

Example 41

(100) ##STR00048##

(101) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0015 g, 0.004 mmol), (R)-L4c (0.0145 g, 0.012 mmol), P(4-MeC.sub.6H.sub.4).sub.3 (0.0129 g, 0.04 mmol), (PhO).sub.2PO.sub.2H (0.0011 g, 0.004 mmol), (±)-1a (0.0425 g, 1 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0218 g, 45%): oil substance; 80% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=6.5 min, t.sub.R (minor)=9.5 min).

Example 42

(102) ##STR00049##

(103) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0016 g, 0.004 mmol), (R)-L4c (0.0144 g, 0.012 mmol), P(4-MeOC.sub.6H.sub.4).sub.3 (0.0149 g, 0.04 mmol), (PhO).sub.2PO.sub.2H (0.0011 g, 0.004 mmol), (±)-1a (0.0416 g, 1 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0128 g, 27%): oil substance; 68% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.6 min, t.sub.R(minor)=9.4 min).

Example 43

(104) ##STR00050##

(105) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0016 g, 0.004 mmol), (R)-L4c (0.0145 g, 0.012 mmol), P(3,5-CF.sub.3C.sub.6H.sub.3).sub.3 (0.0271g, 0.04 mmol), (PhO).sub.2PO.sub.2H (0.0012 g, 0.004 mmol), (±)-1a (0.0413 g, 1 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0071 g, 15%): oil substance; 92% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.7 min, t.sub.R(minor)=9.6 min).

Example 44

(106) ##STR00051##

(107) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0016 g, 0.004 mmol), (R)-L4c (0.0145 g, 0.012 mmol), PPh.sub.3 (0.0105g, 0.04 mmol), organic phosphoric acid (S)-1A (0.0017 g, 0.004 mmol), (±)-1a (0.0397 g, 1 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0226g, 50%): oil substance; 70% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R (major)=6.6 min, t.sub.R (minor)=9.6 min).

Example 45

(108) ##STR00052##

(109) Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0015 g, 0.004 mmol), (R)-L4c (0.0143g, 0.012 mmol), PPh.sub.3 (0.0106 g, 0.04 mmol), organic phosphoric acid (R)-1A (0.0014 g, 0.004 mmol), (±)-1a (0.041 g, 1 mmol), water (72 μL, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1 mL), reacted at 25° C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60˜90° C.)/ether/dichloromethane=30/1/1, petroleum ether (60˜90° C.)/ethyl acetate=8/1) to afford a product: chiral allenic acid (S)-2a (0.0229g, 49%): oil substance; 61% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, λ=214 nm, t.sub.R(major)=6.5 min, t.sub.R(minor)=9.4 min).

(110) Ordinary technicians in this field will understand that within the protection scope of the invention, it is feasible to modify, add and replace the above implementation cases, and none of them is beyond the protection scope of the invention.