PREPARATION METHOD FOR TETRA-SUBSTITUTED ALLENOIC ACID COMPOUND BASED ON PALLADIUM CATALYTIC SYSTEM
20240199521 · 2024-06-20
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Inventors
Cpc classification
C07C51/15
CHEMISTRY; METALLURGY
B01J31/2428
PERFORMING OPERATIONS; TRANSPORTING
B01J31/0259
PERFORMING OPERATIONS; TRANSPORTING
C07C67/293
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C07C57/26
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C07D333/24
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C07D209/86
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B01J2531/0205
PERFORMING OPERATIONS; TRANSPORTING
C07C255/41
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B01J31/2282
PERFORMING OPERATIONS; TRANSPORTING
B01J31/24
PERFORMING OPERATIONS; TRANSPORTING
C07J9/00
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C07C69/76
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C07C51/12
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C07H1/00
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C07C239/20
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C07J17/00
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C07C51/14
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C07C59/52
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International classification
C07C51/12
CHEMISTRY; METALLURGY
C07C59/52
CHEMISTRY; METALLURGY
B01J31/24
PERFORMING OPERATIONS; TRANSPORTING
Abstract
Disclosed in the present invention is a preparation method for a tetra-substituted allenoic acid compound based on a palladium catalytic system, that is, a highly optically active allenoic acid compound having axial chirality is directly constructed in one step by reacting tertiary propargyl alcohol, carbon monoxide and water in an organic solvent under the action of a palladium catalyst, a chiral bisphosphine ligand, an organophosphoric acid, and an organic additive, and the theoretical yield can reach 100%. The method of the present invention is simple to operate, the raw materials and reagents are readily available, the reaction conditions are mild, the substrate universality is wide, the functional group compatibility is good, the reaction has high enantioselectivity (77%?96% ee), and the reaction is well compatible with complex natural products or substrates of a drug molecular skeleton. The highly optically active allenoic acid compound obtained by the present invention can be used as an important intermediate for constructing a ?-butyrolactone compound containing a tetra-substituted chiral quaternary carbon center, tetra-substituted allenol, tetra-substituted allenal, tetra-substituted allenyl ketone, tetra-substituted allenami de and other compounds.
Claims
1. A method for preparing a chiral tetra-substituted allenoic acid compound based on a palladium catalytic system, wherein, in the presence of palladium catalyst, chiral bisphosphine ligand, organophosphoric acid and organic additive, the tertiary propargyl alcohol with different substituents, carbon monoxide and water undergo the asymmetric allenylation reaction in an organic solvent through transition metal catalysis, constructing highly optically active axially chiral allenoic acid compound in one-step synthesis, the reaction process has the following reaction equation (a): ##STR00116## wherein, R.sup.1 is an alkyl, an alkyl with functional group, phenyl, aryl or heterocyclic group; R.sup.2 is an alkyl, an alkyl with functional group, phenyl, aryl or heterocyclic group; R.sup.3 is an alkyl, an alkyl with functional group, phenyl, aryl or heterocyclic group; in R.sup.1, R.sup.2 and R.sup.3, said functional group is selected from carbon-carbon triple bond, hydroxyl, acyl, acyloxy, amide, amino, and silicon group; said aryl group is phenyl group with electron-donating or electron-withdrawing substituents at the ortho, meta, and para positions; said heterocyclyl group is furyl or pyridyl group, or furan or pyridine with electron-donating or electron-withdrawing substituents.
2. The method of claim 1, wherein, R.sup.1 is a C1-C30 alkyl, a C1-C30 alkyl with functional group at the end, phenyl, aryl or heterocyclic group; R.sup.2 is a C1-C10 alkyl, a C1-C10 alkyl with functional group at the end, phenyl, aryl or heterocyclic group; R.sup.3 is C1-C10 alkyl, a C1-C10 alkyl with functional group at the end, phenyl, aryl or heterocyclic group; in R.sup.1, R.sup.2 and R.sup.3, in said C1-C30 alkyl with functional group at the end or said C1-C10 alkyl with functional group at the end, said functional group is selected from carbon-carbon triple bond, hydroxyl, acyl, acyloxy, amide, amino, silicon group; said aryl group is phenyl group with electron-donating or electron-withdrawing substituents at the ortho, meta and para positions, said heterocyclic group is a furanyl or pyridyl group, or furan or pyridine with electron-donating or electron-withdrawing substituents; said electron-withdrawing substituents in the aryl or heterocyclic group include halogen, nitro, ester, carboxyl, acyl, amide, and cyano group, and said electron-donating substituents include alkyl, alkenyl, phenyl, alkoxy group, hydroxyl, amino, silicon group.
3. The method of claim 1, wherein, said method comprises the following steps: 1) adding a palladium catalyst, a chiral bisphosphine ligand and an organophosphoric acid in sequence into a dried reaction tube, plugging the reaction tube with a rubber stopper, connecting the vacuum pump, replacing with argon under argon atmosphere, adding a functionalized tertiary propargyl alcohol, water, organic additives, and a certain volume of organic solvent; freezing the reaction tube in liquid nitrogen bath, inserting carbon monoxide balloon, replacing with carbon monoxide into the reaction system under the atmosphere of carbon monoxide; after freezing and pumping, when the reaction system returns to the room temperature and melts, putting the reaction tube in the preset low-temperature bath at ?20?80? C. or oil bath and stirring for 4-36 hours; wherein, said organic solvent with a certain volume refers to the amount of functionalized tertiary propargyl alcohol shown in equation (a) as a basis, and said dosage of the organic solvent is 1.0-10.0 mL/mmol; 2) after the completion of the reaction in step 1), raising the reaction tube from the oil bath, after returning to the room temperature, adding a certain volume of ethyl acetate into the reaction tube, filtering the resulting 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 highly optically active axially chiral allenoic acid compounds; wherein, the certain volume of the ethyl acetate refers to the amount of functionalized tertiary propargyl alcohol shown in equation (a) as a basis, said amount of ethyl acetate is 1.0-100 mL/mmol.
4. The method of claim 1, wherein, said 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, said chiral diphosphine ligand is selected from one or more of (R)-L1?(R)-L4 and its enantiomer (S)-L1?(S)-L4 in the following structures; wherein, Ar is a phenyl, an aryl or heterocyclic group; said aryl group is a phenyl group substituted by alkyl or alkoxy group at the ortho, meta, and para positions; said heterocyclic group is thiophene, furan, or pyridine and thiophene substituted by alkyl or alkoxy group, furan substituted by alkyl or alkoxy group, or pyridine substituted by alkyl or alkoxy group: ##STR00117##
6. The method of claim 5, wherein said 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, 4-alkylphenyl or phenyl group; ##STR00118##
7. The method of claim 1, wherein said organophosphoric acid is selected from any one or more of organophosphoric acid 1, organophosphoric acid 2, organophosphoric acid 3, the structure of which is as follows; wherein, R.sup.4 is C1?C6 alkyl, phenyl or aryl group; said aryl group is a phenyl group substituted by C1?C6 alkyl at the ortho, meta, and para positions; R.sup.5 is hydrogen, C1?C6 alkyl, phenyl or aryl group; said aryl group is a phenyl group substituted by C1?C6 alkyl at the ortho, meta, and para positions; ##STR00119##
8. The method of claim 1, wherein, said organic additive is selected from any one or more of 1,1-bis(diphenylphosphine)methane, 1,2-bis(diphenylphosphine)ethane, 1,3-bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, 1,1-bis(diphenylphosphine)ferrocene, bis(2-diphenylphosphine)ether, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,1-binaphthyl-2,2-bisdiphenylphosphine, triphenylphosphine, tri(4-methoxyphenyl)phosphine, tri(4-methylphenyl)phosphine, tri(4-fluorophenyl)phosphine, tris(4-trifluoromethylphenyl)phosphine, dichloromethane, dibromomethane, chloroform, bromoform, carbon tetrachloride, bromoethane, bromobutane, benzene, fluorobenzene, 1,4-difluorobenzene, hexafluorobenzene, chlorobenzene, 1,4-dichlorobenzene, bromobenzene, 1,4-dibromobenzene, 4-methoxybromobenzene, 4-methylbromobenzene, 4-fluorobromobenzene, 4-trifluoromethylbromobenzene, iodobenzene, trifluorotoluene, aniline, benzenesulfonic acid, phenol, phenylboronic acid; and/or, said organic solvent is selected from any one or more of N-methyl pyrrolidone, 1,4-dioxane, tetrahydrofuran, acetonitrile, methyl tert-butyl ether, fluorobenzene, chlorobenzene, bromobenzene, iodobenzene, toluene, 1,2-xylene, 1,3-xylene, 1,4-xylene, mesitylene, 4-ethyltoluene, 1,4-diethylbenzene, triethylbenzene, trifluorotoluene, dichloromethane, dibromomethane, 1,1-dichloroethane, 1,2-dichloroethane, 1,2-dibromoethane, chloroform, acetic acid, N,N-dimethylformamide and dimethyl sulfoxide.
9. The method of claim 1, wherein, the molar ratio of tertiary propargyl alcohol (?1) with different substituents, water, palladium catalyst, chiral bisphosphine ligand, organophosphoric acid, and organic additives is 1.0:(1.0-30.0):(0.005-0.1):(0.005-0.1):(0.01-0.3):(0.1-30); and/or, the reaction temperature is ?20 100? C.; and/or, the dosage of the organic solvent is 1.0-10.0 mL/mmol, based on the dosage of functionalized tertiary propargyl alcohol (?1).
10. A class of highly optically active axially chiral allenoic acid compound, wherein, the structure is as (R)-2, (S)-2 shown: ##STR00120## wherein, R.sup.1 is an alkyl, an alkyl with functional group, phenyl, aryl or heterocyclic group; R.sup.2 is an alkyl, an alkyl with functional group, phenyl, aryl or heterocyclic group; R.sup.3 is an alkyl, an alkyl with functional group, phenyl, aryl or heterocyclic groups; in R.sup.1, R.sup.2 and R.sup.3, said functional group is selected from carbon-carbon triple bond, hydroxyl, acyl, acyloxy, amide, amino, and silicon group; said aryl group is phenyl group with electron-donating or electron-withdrawing substituents at the ortho, meta, and para positions; said heterocyclyl group is furyl or pyridyl group, or furan or pyridine with electron-donating or electron-withdrawing substituents.
11. The compound of claim 10, wherein, R.sup.1 is a C1-C30 alkyl, a C1-C30 alkyl with functional group at the end, phenyl, aryl or heterocyclic group; R.sup.2 is a C1-C10 alkyl, a C1-C10 alkyl with functional group at the end, phenyl, aryl or heterocyclic group; R.sup.3 is C1-C10 alkyl, a C1-C10 alkyl with functional group at the end, phenyl, aryl or heterocyclic group; in R.sup.1, R.sup.2 and R.sup.3, in the C1-C30 alkyl with functional group at the end or the C1-C10 alkyl with functional group at the end, the functional group is selected from carbon-carbon triple bond, hydroxyl, acyl, acyloxy, amide, amino, silicon group; said aryl group is phenyl group with electron-donating or electron-withdrawing substituents at the ortho, meta and para positions, said heterocyclic group is a furanyl or pyridyl group, or furan or pyridine with electron-donating or electron-withdrawing substituents; said electron-withdrawing substituents in the aryl or heterocyclic group include halogen, nitro, ester, carboxyl, acyl, amide, and cyano groups, and the electron-donating substituents include alkyl, alkenyl, phenyl, alkoxy group, hydroxyl, amino, silicon group.
12. A highly optically active axially chiral allenoic acid compound according to claim 10 for use to preparing ?-butyrolactone compound containing a tetra-substituted chiral quaternary carbon center, tetra-substituted allenol, tetra-substituted allenal, tetra-substituted allenyl ketone, tetra-substituted allenamide compounds.
13. The method of claim 2, wherein, said 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.
14. The method of claim 3, wherein, said 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.
15. The method of claim 2, wherein, said chiral diphosphine ligand is selected from one or more of (R)-L1?(R)-L4 and its enantiomer (S)-L1(S)-L4 in the following structures; wherein, Ar is a phenyl, an aryl or heterocyclic group; said aryl group is a phenyl group substituted by alkyl or alkoxy group at the ortho, meta, and para positions; said heterocyclic group is thiophene, furan, or pyridine and thiophene substituted by alkyl or alkoxy group, furan substituted by alkyl or alkoxy group, or pyridine substituted by alkyl or alkoxy group; ##STR00121##
16. The method of claim 3, wherein, said chiral diphosphine ligand is selected from one or more of (R)-L1?(R)-L4 and its enantiomer (S)-L1?(S)-L4 in the following structures; wherein, Ar is a phenyl, an aryl or heterocyclic group; said aryl group is a phenyl group substituted by alkyl or alkoxy group at the ortho, meta, and para positions; said heterocyclic group is thiophene, furan, or pyridine and thiophene substituted by alkyl or alkoxy group, furan substituted by alkyl or alkoxy group, or pyridine substituted by alkyl or alkoxy group; ##STR00122##
17. The method of claim 2, wherein said organophosphoric acid is selected from any one or more of organophosphoric acid 1, organophosphoric acid 2, organophosphoric acid 3, the structure of which is as follows; wherein, R.sup.4 is C1?C6 alkyl, phenyl or aryl group; said aryl group is a phenyl group substituted by C1?C6 alkyl at the ortho, meta, and para positions; R.sup.5 is hydrogen, C1?C6 alkyl, phenyl or aryl group; said aryl group is a phenyl group substituted by C1?C6 alkyl at the ortho, meta, and para positions; ##STR00123##
18. The method of claim 3, wherein said organophosphoric acid is selected from any one or more of organophosphoric acid 1, organophosphoric acid 2, organophosphoric acid 3, the structure of which is as follows; wherein, R.sup.4 is C1?C6 alkyl, phenyl or aryl group; said aryl group is a phenyl group substituted by C1?C6 alkyl at the ortho, meta, and para positions; R.sup.5 is hydrogen, C1?C6 alkyl, phenyl or aryl group; said aryl group is a phenyl group substituted by C1?C6 alkyl at the ortho, meta, and para positions; ##STR00124##
19. The method of claim 2, wherein, said organic additive is selected from any one or more of 1,1-bis(diphenylphosphine)methane, 1,2-bis(diphenylphosphine)ethane, 1,3-bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, 1,1-bis(diphenylphosphine)ferrocene, bis(2-diphenylphosphine)ether, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,1-binaphthyl-2,2-bisdiphenylphosphine, triphenylphosphine, tri(4-methoxyphenyl)phosphine, tri(4-methylphenyl)phosphine, tri(4-fluorophenyl)phosphine, tris(4-trifluoromethylphenyl)phosphine, dichloromethane, dibromomethane, chloroform, bromoform, carbon tetrachloride, bromoethane, bromobutane, benzene, fluorobenzene, 1,4-difluorobenzene, hexafluorobenzene, chlorobenzene, 1,4-dichlorobenzene, bromobenzene, 1,4-dibromobenzene, 4-methoxybromobenzene, 4-methylbromobenzene, 4-fluorobromobenzene, 4-trifluoromethylbromobenzene, iodobenzene, trifluorotoluene, aniline, benzenesulfonic acid, phenol, phenylboronic acid; and/or, said organic solvent is selected from any one or more of N-methyl pyrrolidone, 1,4-dioxane, tetrahydrofuran, acetonitrile, methyl tert-butyl ether, fluorobenzene, chlorobenzene, bromobenzene, iodobenzene, toluene, 1,2-xylene, 1,3-xylene, 1,4-xylene, mesitylene, 4-ethyltoluene, 1,4-diethylbenzene, triethylbenzene, trifluorotoluene, dichloromethane, dibromomethane, 1,1-dichloroethane, 1,2-dichloroethane, 1,2-dibromoethane, chloroform, acetic acid, N,N-dimethylformamide and dimethyl sulfoxide.
20. The method of claim 3, wherein, said organic additive is selected from any one or more of 1,1-bis(diphenylphosphine)methane, 1,2-bis(diphenylphosphine)ethane, 1,3-bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, 1,1-bis(diphenylphosphine)ferrocene, bis(2-diphenylphosphine)ether, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,1-binaphthyl-2,2-bisdiphenylphosphine, triphenylphosphine, tri(4-methoxyphenyl)phosphine, tri(4-methylphenyl)phosphine, tri(4-fluorophenyl)phosphine, tris(4-trifluoromethylphenyl)phosphine, dichloromethane, dibromomethane, chloroform, bromoform, carbon tetrachloride, bromoethane, bromobutane, benzene, fluorobenzene, 1,4-difluorobenzene, hexafluorobenzene, chlorobenzene, 1,4-dichlorobenzene, bromobenzene, 1,4-dibromobenzene, 4-methoxybromobenzene, 4-methylbromobenzene, 4-fluorobromobenzene, 4-trifluoromethylbromobenzene, iodobenzene, trifluorotoluene, aniline, benzenesulfonic acid, phenol, phenylboronic acid; and/or, said organic solvent is selected from any one or more of N-methyl pyrrolidone, 1,4-dioxane, tetrahydrofuran, acetonitrile, methyl tert-butyl ether, fluorobenzene, chlorobenzene, bromobenzene, iodobenzene, toluene, 1,2-xylene, 1,3-xylene, 1,4-xylene, mesitylene, 4-ethyltoluene, 1,4-diethylbenzene, triethylbenzene, trifluorotoluene, dichloromethane, dibromomethane, 1,1-dichloroethane, 1,2-dichloroethane, 1,2-dibromoethane, chloroform, acetic acid, N,N-dimethylformamide and dimethyl sulfoxide.
Description
PREFERRED EMBODIMENTS OF THE INVENTION
[0070] 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 (including their enantiomers) of chiral diphosphine ligands involved in all the examples are as follows:
##STR00037##
[0071] The specific structural formula and the corresponding number (including their enantiomers) of organophosphoric acid involved in all the examples are as follows:
##STR00038##
EXAMPLE 1
[0072] ##STR00039##
[0073] Wherein, mol refers to mole, PhBr refers to bromobenzene, PhMe refers to toluene, CO balloon refers to carbon monoxide balloon, ee refers to the percentage of enantiomeric excess.
[0074] [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0148 g, 0.012 mmol), (S)-CPA-1 (0.0039 g, 0.005 mmol) were added in sequence to a dry Schlenk reaction tube. The reaction tube was plugged with a rubber stopper, and then connected with the vacuum pump, and replaced with the argon three times under an argon atmosphere. And under the protection of the argon, tertiary propargyl alcohol (?)-1a (0.0402 g, 0.2 mmol), toluene (0.8 mL), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol) and water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol) were added. After the argon was closed, the reaction tube was placed in a liquid nitrogen bath to freeze for 3 minutes, inserted by carbon monoxide balloon (about 1 liter), replaced with carbon monoxide three times under a carbon monoxide atmosphere, then the liquid nitrogen bath was removed. After the reaction system returned to the room temperature and melted into liquid, the reaction tube was placed in an oil bath that had been preheated to 50? C. and stirred for 12 hours. The reaction was taken out of the oil bath, and after returning to room temperature, added with H.sub.2O.sub.2 (8 ?L, d=1.13 g/mL, 30 wt. % in H.sub.2O, 0.0027 g, 0.08 mmol). After stirred at room temperature for 30 minutes, the reaction solution was diluted by adding ethyl acetate (1 mL), and the resulting mixture was filtered through a short silica gel column (1 cm), washed with ethyl acetate (5 mL), concentrated, and subjected to flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to to afford a product: chiral allenoic acid (S)-2a (0.0385 g, 84%): solid; 93% ee (HPLC conditions: AS-H column, hexane/i-PrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R (major)=8.7 min, t.sub.R(minor)=12.1 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.44-7.27 (m, 4 H, ArH), 7.27-7.21 (m, 1 H, ArH), 2.32 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.19 (s, 3 H, CH.sub.3), 1.52-1.40 (m, 2 H, CH.sub.2), 1.40-1.29 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.6, 172.8, 135.0, 128.5, 127.6, 126.1, 105.2, 101.8, 30.2, 28.3, 22.2, 16.3, 13.8.
EXAMPLE 2
[0075] ##STR00040##
[0076] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0037 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0366 g, 0.03 mmol), (S)-CPA-1 (0.0601 g, 0.075 mmol), (?)-1b (0.1104 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 10/1) to afford a product: chiral allenoic acid (S)-2b (0.0841 g, 68%): oil; 88% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.5 min, t.sub.R(minor)=13.0 min); [?].sub.D.sup.27=+37.5 (c=1.06, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.33 (td, J.sub.1=7.8 Hz, J.sub.2=1.7 Hz, 1 H, ArH), 7.27-7.21 (m, 1 H, ArH), 7.12 (td, J.sub.1=7.5 Hz, J.sub.2=1.1 Hz, 1 H, ArH), 7.07-7.00 (m, 1 H, ArH), 2.36-2.24 (m, 2 H, CH.sub.2), 2.24-2.13 (m, 3 H, CH.sub.3), 1.53-1.41 (m, 2 H, CH.sub.2), 1.39-1.27 (m, 2 H, CH.sub.2), 0.89 (t, J=7.2 Hz, 2 H, CH.sub.2); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.9 (d, J=1.6 Hz), 173.1, 160.3 (d, J=248.8 Hz), 129.1 (d, J=8.7 Hz), 128.9 (d, J=3.1 Hz), 124.1 (d, J=3.2 Hz), 123.6 (d, J=11.9 Hz), 116.0 (d, J=22.1 Hz), 100.4, 99.9 (d, J=1.6 Hz), 30.0, 28.2, 22.2, 17.9 (d, J=2.4 Hz), 13.8; .sup.19F NMR (376 MHz, CDCl.sub.3): ?=?112.1; IR (neat): ?=2957, 2929, 2859, 1943, 1681, 1493, 1279, 1079 cm.sup.?1; MS (70 eV, EI) m/z (%): 248 (M.sup.+, 2.21), 161 (100); HRMS calcd for C.sub.15H.sub.17FO.sub.2 [M.sup.+]: 248.1207, found: 248.1207.
EXAMPLE 3
[0077] ##STR00041##
[0078] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0037 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0367 g, 0.03 mmol), (S)-CPA-1 (0.0402 g, 0.05 mmol), (?)-1c (0.1104 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 10/1) to afford a product: chiral allenoic acid (S)-2c (0.0847 g, 68%): white solid; 91% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.0 min, t.sub.R(minor)=11.8 min); [?].sub.D.sup.27=+18.0 (c=1.00, CHCl.sub.3); melting point: 104.1-105.2? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.34-7.23 (m, 1 H, ArH), 7.16 (d, J=8.0 Hz, 1 H, ArH), 7.07 (dt, J.sub.1=10.4 Hz, J.sub.2=2.0 Hz, 1 H, ArH), 6.94 (td, J.sub.1=7.9 Hz, J.sub.2=2.3 Hz, 1 H, ArH), 2.33 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.17 (s, 3 H, CH.sub.3), 1.51-1.41 (m, 2 H, CH.sub.2), 1.41-1.30 (m, 2 H, CH.sub.2), 0.88 (t, J=7.4 Hz, 2 H, CH.sub.2); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.6, 172.7, 163.1 (d, J=244.1 Hz), 137.5 (d, J=7.1 Hz), 129.9 (d, J=8.6 Hz), 121.7 (d, J=2.4 Hz), 114.4 (d, J=21.3 Hz), 112.9 (d, J=22.9 Hz), 104.5 (d, J=3.1 Hz), 102.3, 30.1, 28.2, 22.2, 16.2, 13.8; .sup.19F NMR (376 MHz, CDCl.sub.3): ?=?113.6; IR (neat): ?=2961, 2929, 2863, 1937, 1685, 1422, 1264, 1089, 1021 cm.sup.?1; MS (70 eV, EI) m/z (%): 248 (M.sup.+, 3.61), 161 (100); Anal. Calcd. for C.sub.15H.sub.17FO.sub.2: C 72.56, H 6.90; found C 72.50, H 7.14.
EXAMPLE 4
[0079] ##STR00042##
[0080] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0036 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0368 g, 0.03 mmol), (S)-CPA-1 (0.0101 g, 0.0125 mmol), (?)-1d (0.1104 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2d (0.0911 g, 73%): white solid; 94% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.9 min, t.sub.R(minor)=11.9 min); [?].sub.D.sup.28=+18.7 (c=1.00, CHCl.sub.3); melting point: 113.0-114.0? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.41-7.29 (m, 2 H, ArH), 7.09-6.96 (m, 2 H, ArH), 2.32 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.17 (s, 3 H, CH.sub.3), 1.51-1.40 (m, 2 H, CH.sub.2), 1.40-1.29 (m, 2 H, CH.sub.2), 0.88 (t, J=7.4 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.3 (d, J=2.4 Hz), 172.8, 162.3 (d, J=245.7 Hz), 131.0 (d, J=3.2 Hz), 127.7 (d, J=8.7 Hz), 115.5 (d, J=21.3 Hz), 104.4, 101.9, 30.2, 28.3, 22.2, 16.5, 13.8; .sup.19F NMR (376 MHz, CDCl.sub.3): ?=?115.0; IR (neat): ?=2940, 2868, 1939, 1683, 1507, 1284, 1233 cm.sup.?1; MS (70 eV, EI) m/z (%): 248 (M.sup.+, 2.68), 161 (100); Anal. Calcd. for C.sub.15H.sub.17FO.sub.2: C 72.56, H 6.90; found C 72.72, H 7.14.
EXAMPLE 5
[0081] ##STR00043##
[0082] Operations were conducted by referring to Example 1 [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0149 g, 0.0012 mmol), (S)-CPA-1 (0.0081 g, 0.01 mmol), (?)-1e (0.0471 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2e (0.0415 g, 79%): white solid; 93% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.7 min, t.sub.R(minor)=13.3 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.30 (s, 4 H, ArH), 2.32 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.17 (s, 3 H, CH.sub.3), 1.49-1.40 (m, 2 H, CH.sub.2), 1.40-1.29 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.4, 172.3, 133.6, 133.4, 128.7, 127.3, 104.4, 102.1, 30.2, 28.3, 22.2, 16.3, 13.8.
EXAMPLE 6
[0083] ##STR00044##
[0084] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0149 g, 0.0012 mmol), (S)-CPA-1 (0.008 g, 0.01 mmol), (?)-1f (0.0565 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2f (0.0499 g, 80%): white solid; 94% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=10.5 min, t.sub.R(minor)=14.8 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.50-7.41 (m, 2 H, ArH), 7.26-7.19 (m, 2 H, ArH), 2.32 (d, J=7.4 Hz, 2 H, CH.sub.2), 2.16 (s, 3 H, CH.sub.3), 1.49-1.39 (m, 2 H, CH.sub.2), 1.39-1.29 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.4, 172.4, 134.1, 131.7, 127.6, 121.5, 104.5, 102.2, 30.2, 28.2, 22.2, 16.2, 13.8.
EXAMPLE 7
[0085] ##STR00045##
[0086] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0165 g, 0.0012 mmol), (S)-CPA-1 (0.0159 g, 0.02 mmol), (?)-1g (0.0519 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2g (0.0427 g, 74%): white solid; 94% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=10.5 min, t.sub.R(minor)=14.8 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.50-7.41 (m, 2 H, ArH), 7.26-7.19 (m, 2 H, ArH), 2.32 (d, J=7.4 Hz, 2 H, CH.sub.2), 2.16 (s, 3 H, CH.sub.3), 1.49-1.39 (m, 2 H, CH.sub.2), 1.39-1.29 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.4, 172.4, 134.1, 131.7, 127.6, 121.5, 104.5, 102.2, 30.2, 28.2, 22.2, 16.2, 13.8.
EXAMPLE 8
[0087] ##STR00046##
[0088] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0037 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0368 g, 0.03 mmol), (S)-CPA-1 (0.0403 g, 0.05 mmol), (?)-1h (0.1349 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 65? C. for 24 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=10/1, then 15/1) to afford a product: chiral allenoic acid (S)-2h (0.0911 g, 73%): white solid; 90% ee (HPLC conditions: AD-H column, hexane/.sup.iPrOH=99/1, 1.0 mL/min, ?=214 nm, t.sub.R(minor)=17.8 min, t.sub.R(major)=27.0 min); [?].sub.D.sup.26=+19.2 (c=1.00, CHCl.sub.3); melting point: 101.4-102.4? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.59 (d, J=8.4 Hz, 2 H, ArH), 7.48 (d, J=8.4 Hz, 2 H, ArH), 2.34 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.21 (s, 3 H, CH.sub.3), 1.51-1.41 (m, 2 H, CH.sub.2), 1.40-1.30 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.9, 172.5, 139.0, 129.5 (q, J=32.4 Hz), 126.3, 125.5 (q, J=3.7 Hz), 124.1 (q, J=270.2 Hz), 104.5, 102.5, 30.2, 28.2, 22.2, 16.2, 13.8; .sup.19F NMR (376 MHz, CDCl.sub.3): ?=?63.1; IR (neat): ?=2957, 2939, 2867, 1943, 1689, 1418, 1327, 1267, 1125, 1075 cm.sup.?1; MS (70 eV, EI) m/z (%): 299 (M.sup.++1, 1.65), 298 (M.sup.+, 9.88), 211 (100); Anal. Calcd. for C.sub.16H.sub.17F.sub.3O.sub.2: C 64.42, H 5.74; found C 64.60, H 5.87.
EXAMPLE 9
[0089] ##STR00047##
[0090] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0036 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0369 g, 0.03 mmol), (S)-CPA-1 (0.1202 g, 0.15 mmol), (?)-1i (0.1137 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 65? C. for 24 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ether/dichloromethane=10/1/1, petroleum ether (60?90? C.)/ethyl acetate=15/1) to afford a product: chiral allenoic acid (S)-21 (0.0772 g, 60%): white solid; 84% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=90/10, 1.0 mL/min, ?=214 nm, t.sub.R(minor)=10.7 min, t.sub.R(major)=12.8 min); [?].sub.D.sup.25=+17.1 (c=1.00, CHCl.sub.3); melting point: (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.63 (d, J=8.4 Hz, 2 H, ArH), 7.47 (d, J=8.4 Hz, 2 H, ArH), 2.35 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.20 (s, 3 H, CH.sub.3), 1.50-1.40 (m, 2 H, CH.sub.2), 1.40-1.29 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=213.1, 172.2, 140.1, 132.3, 126.5, 118.7, 110.9, 104.4, 102.8, 30.1, 28.2, 22.2, 16.0, 13.7; IR (neat): ?=2962, 2930, 2862, 2227, 1939, 1693, 1419, 1285, 1059 cm.sup.?1; MS (70 eV, EI) m/z (%): 256 (M.sup.++1, 1.41), 255 (M.sup.+, 4.50), 168 (100); Anal. Calcd. for C.sub.16H.sub.17NO.sub.2: C 75.27, H 6.71; found C 75.16, H 6.65.
EXAMPLE 10
[0091] ##STR00048##
[0092] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0149 g, 0.0012 mmol), (S)-CPA-1 (0.004 g, 0.005 mmol), (?)-1j (0.0465 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 14 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2j (0.0416 g, 80%): white solid; 91% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=11.9 min, t.sub.R(minor)=16.1 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.26 (t, J=8.0 Hz, 1 H, ArH), 6.98 (d, J=8.0 Hz, 1 H, ArH), 6.92 (t, J=2.0 Hz, 1 H, ArH), 6.81 (dd, Ji =8.4 Hz, J.sub.2=2.4 Hz, 1 H, ArH), 3.81 (s, 3 H, OCH.sub.3), 2.32 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.18 (s, 3 H, CH.sub.3), 1.52-1.41 (m, 2 H, CH.sub.2), 1.41-1.30 (m, 2 H, CH.sub.2), 0.88 (t, J=7.4 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.4, 159.8, 136.6, 129.5, 118.6, 112.8, 112.0, 105.1, 101.8, 55.2, 30.2, 28.3, 22.3, 16.4, 13.8.
EXAMPLE 11
[0093] ##STR00049##
[0094] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0148 g, 0.0012 mmol), (S)-CPA-1 (0.0041 g, 0.005 mmol), (?)-1k (0.0432 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 65? C. for 5 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 15/1) to afford a product: chiral allenoic acid (S)-2k (0.0319 g, 65%): white solid; 87% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=7.3 min, t.sub.R(minor)=9.6 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.29-7.12 (m, 3 H, ArH), 7.07 (d, J=7.2 Hz, 1 H, ArH), 2.41-2.27 (m, 5 H, CH.sub.2 and CH.sub.3), 2.18 (s, 3 H, CH.sub.3), 1.52-1.41 (m, 2 H, CH.sub.2), 1.40-1.29 (m, 2 H, CH.sub.2), 0.88 (t, J=7.4 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.7, 138.1, 134.9, 128.42, 128.38, 126.7, 123.2, 105.2, 101.6, 30.2, 28.3, 22.3, 21.5, 16.4, 13.8.
EXAMPLE 12
[0095] ##STR00050##
[0096] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0147 g, 0.0012 mmol), (S)-CPA-1 (0.0039 g, 0.005 mmol), (?)-1l (0.043 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 10 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 15/1) to afford a product: chiral allenoic acid (S)-2l (0.0325 g, 67%): white solid; 95% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.4 min, t.sub.R(minor)=10.9 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.27 (d, J=8.0 Hz, 2 H, ArH), 7.15 (d, J=8.0 Hz, 2 H, ArH), 2.38-2.26 (m, 5 H, CH.sub.2 and CH.sub.3), 2.17 (s, 3 H, CH.sub.3), 1.50-1.40 (m, 2 H, CH.sub.2), 1.39-1.29 (m, 2 H, CH.sub.2), 0.87 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.9, 137.4, 132.0, 129.2, 126.0, 105.1, 101.7, 30.2, 28.3, 22.3, 21.1, 16.3, 13.8.
EXAMPLE 13
[0097] ##STR00051##
[0098] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0038 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0369 g, 0.03 mmol), (S)-CPA-1 (0.0101 g, 0.0125 mmol), (?)-1m (0.1223 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 10 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1) to afford a product: chiral allenoic acid (S)-2m (0.0821 g, 60%): white solid; 95% ee (HPLC conditions: AD-H column, hexane/.sup.iPrOH=99/1, 1.0 mL/min, ?=214 nm, t.sub.R(major)=16.7 min, t.sub.R(minor)=18.6 min); [?].sub.D.sup.27=+20.7 (c=1.01, CHCl.sub.3); melting point: 79.6-80.2? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.31 (d, J=8.4 Hz, 2 H, ArH), 7.20 (d, J=8.4 Hz, 2 H, ArH), 2.90 (heptet, J=6.8 Hz, 1 H, CH), 2.32 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.17 (s, 3 H, CH.sub.3), 1.51-1.40 (m, 2 H, CH.sub.2), 1.40-1.29 (m, 2 H, CH.sub.2), 1.24 (d, J=6.8 Hz, 6 H, 2 x CH.sub.3), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.6, 172.9, 148.4, 132.4, 126.6, 126.0, 105.0, 101.7, 33.8, 30.2, 28.3, 23.90, 23.87, 22.3, 16.3, 13.8; IR (neat): ?=2958, 2927, 1941, 1679, 1419, 1278, 1067 cm.sup.?1; MS (70 eV, EI) m/z (%): 272 (M.sup.+, 3.98), 143 (100); Anal. Calcd. for C.sub.18H.sub.24O.sub.2: C 79.37, H 8.88; found C 79.32, H 8.82.
EXAMPLE 14
[0099] ##STR00052##
[0100] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0036 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0367 g, 0.03 mmol), (S)-CPA-1 (0.0102 g, 0.0125 mmol), (?)-1n (0.1375 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 10 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1) to afford a product: chiral allenoic acid (S)-2n (0.1372 g, 91%): white solid; 96% ee (HPLC conditions: AD-H column, hexane/.sup.iPrOH=99/1, 1.0 mL/min, ?=214 nm, t.sub.R(major)=10.6 min, t.sub.R(minor)=12.9 min); [?].sub.D.sup.29=+20.3 (c=1.00, CHCl.sub.3); melting point: 80.8-81.3? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.50 (d, J=8.0 Hz, 2 H, ArH), 7.37 (d, J=8.4 Hz, 2 H, ArH), 2.32 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.18 (s, 3 H, CH.sub.3), 1.53-1.40 (m, 2 H, CH.sub.2), 1.40-1.29 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3), 0.26 (s, 9 H, 3 x CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=213.7, 173.9, 140.9, 136.5, 134.6, 126.3, 106.2, 102.9, 31.2, 29.3, 23.3, 17.2, 14.8, ?0.2; IR (neat): ?=2956, 2928, 1942, 1682, 1416, 1249, 1058 cm.sup.?1; MS (70 eV, EI) m/z (%): 303 (M.sup.++1, 1.80), 302 (M.sup.+, 7.35), 73 (100); Anal. Calcd. for C.sub.18H.sub.26O.sub.2Si: C 71.47, H 8.66; found C 71.45, H 8.55.
EXAMPLE 15
[0101] ##STR00053##
[0102] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0149 g, 0.0012 mmol), (S)-CPA-1 (0.0041 g, 0.005 mmol), (?)-1o (0.0503 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2o (0.0414 g, 74%): white solid; 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=11.3 min, t.sub.R(minor)=15.0 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.87-7.71 (m, 4 H, ArH), 7.56-7.40 (m, 3 H, ArH), 2.37 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.31 (s, 3 H, CH.sub.3), 1.54-1.43 (m, 2 H, CH.sub.2), 1.42-1.31 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=213.1, 172.4, 133.5, 132.8, 132.4, 128.09, 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.
EXAMPLE 16
[0103] ##STR00054##
[0104] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0148 g, 0.0012 mmol), (S)-CPA-1 (0.0015 g, 0.002 mmol), (?)-1p (0.0503 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 3 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2p (0.0321 g, 68%): white solid; 93% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=11.5 min, t.sub.R(minor)=15.9 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.28 (dd, J.sub.1=5.2 Hz, J.sub.2=2.8 Hz, 1 H, one proton from thienyl), 7.15 (d, J.sub.1=2.8 Hz, J.sub.2=1.2 Hz, 1 H, one proton from thienyl), 7.04 (d, J.sub.1=5.0 Hz, J.sub.2=1.0 Hz, 1 H, one proton from thienyl), 2.31 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.17 (s, 3H, CH.sub.3), 1.50-1.40 (m, 2H, CH.sub.2), 1.40-1.30 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.8, 172.2, 136.5, 126.3, 125.9, 120.6, 101.4, 101.3, 30.3, 28.4, 22.2, 16.7, 13.8.
EXAMPLE 17
[0105] ##STR00055##
[0106] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0149 g, 0.0012 mmol), (S)-CPA-1 (0.004 g, 0.002 mmol), (?)-1q (0.042 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 18 hours. No target chiral allenoic acid product (S)-2q was formed.
EXAMPLE 18
[0107] ##STR00056##
[0108] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0037 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0369 g, 0.03 mmol), (S)-CPA-1 (0.0101 g, 0.0125 mmol), (?)-1r (0.0943 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 15/1) to afford a product: chiral allenoic acid (S)-2r (0.0948 g, 88%): white solid; 91% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.4 min, t.sub.R(minor)=12.7 min); [?].sub.D.sup.26=+49.4 (c=1.01, CHCl.sub.3); melting point: 88.5-89.6? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.38 (d, J=7.6 Hz, 2 H, ArH), 7.33 (t, J=7.4 Hz, 2 H, ArH), 7.24 (t, J=7.2 Hz, 1 H, ArH), 2.30 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.19 (s, 3 H, CH.sub.3), 1.51 (sextet, J=7.4 Hz, 2 H, CH.sub.2), 0.92 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.7, 173.0, 135.0, 128.5, 127.5, 126.1, 105.2, 101.6, 30.6, 21.4, 16.3, 13.7; IR (neat): ?=2961, 2929, 1942, 1682, 1415, 1263, 1066 cm.sup.?1; MS (70 eV, EI) m/z (%): 217 (M.sup.++1, 3.86), 216 (M.sup.+, 24.20), 143 (100); Anal. Calcd. for Ci4H1602: C 77.75, H 7.46; found C 77.89, H 7.63.
EXAMPLE 19
[0109] ##STR00057##
[0110] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0148 g, 0.0012 mmol), (S)-CPA-1 (0.0118 g, 0.015 mmol), (?)-1s (0.0531 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2s (0.0449 g, 77%): white solid; 96% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 0.5 mL/min, ?=214 nm, t.sub.R(major)=23.1 min, t.sub.R(minor)=26.0 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.46 (d, J=8.4 Hz, 2 H, ArH), 7.25 (d, J=8.4 Hz, 2 H, ArH), 2.79 (heptet, J=6.8 Hz, 1 H, CH), 2.17 (s, 3 H, CH.sub.3), 1.09 (d, J=6.8 Hz, 6 H, 2 x CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=211.2, 171.9, 134.0, 131.7, 127.5, 121.5, 109.0, 105.9, 28.2, 22.1, 22.0, 16.3.
EXAMPLE 20
[0111] ##STR00058##
[0112] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0149 g, 0.0012 mmol), (S)-CPA-1 (0.004 g, 0.015 mmol), (?)-1t (0.0346 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 65? C. for 4 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2t (0.0346 g, 70%): white solid; 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=7.5 min, t.sub.R(minor)=9.9 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.44-7.28 (m, 4 H, ArH), 7.28-7.22 (m, 1 H, ArH), 2.33 (t, J=8.0 Hz, 2 H, CH.sub.3), 2.19 (s, 3 H, CH.sub.3), 1.65-1.50 (m, 1 H, CH), 1.42-1.30 (m, 2 H, CH.sub.2), 0.87 (t, J=6.0 Hz, 6 H, 2 x CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.4, 172.6, 135.0, 128.5, 127.6, 126.1, 105.3, 102.0, 37.1, 27.7, 26.6, 22.44, 22.40, 16.3.
EXAMPLE 21
[0113] ##STR00059##
[0114] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0147 g, 0.0012 mmol), (S)-CPA-1 (0.0041 g, 0.015 mmol), (?)-1u (0.0431 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2u (0.0434 g, 89%): white solid; 92% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=7.8 min, t.sub.R(minor)=12.9 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.44-7.30 (m, 4 H, ArH), 7.28-7.22 (m, 1 H, ArH), 2.32 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.19 (s, 3 H, CH.sub.3), 1.54-1.41 (m, 2 H, CH.sub.2), 1.33-1.23 (m, 4 H, 2 x CH.sub.2), 0.84 (t, J=7.0 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.6, 172.7, 135.0, 128.5, 127.6, 126.1, 105.2, 101.8, 31.3, 28.5, 27.7, 22.4, 16.3, 14.0.
EXAMPLE 22
[0115] ##STR00060##
[0116] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0148 g, 0.0012 mmol), (S)-CPA-1 (0.0041 g, 0.015 mmol), (?)-1v (0.0485 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2v (0.0405 g, 79%): white solid; 92% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=7.3 min, t.sub.R(minor)=12.2 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.41-7.29 (m, 4 H, ArH), 7.28-7.22 (m, 1 H, ArH), 2.32 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.19 (s, 3H, CH.sub.3), 1.53-1.41 (m, 2 H, CH.sub.2), 1.36-1.15 (m, 6 H, 3 x CH.sub.2), 0.84 (t, J=6.8 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.6, 172.7, 135.0, 128.5, 127.6, 126.1, 105.2, 101.8, 31.6, 28.8, 28.6, 28.0, 22.6, 16.3, 14.0.
EXAMPLE 23
[0117] ##STR00061##
[0118] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0038 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0367 g, 0.03 mmol), (S)-CPA-1 (0.0101 g, 0.0125 mmol), (?)-1w (0.1292 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 10 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1) to afford a product: chiral allenoic acid (S)-2w (0.0812 g, 57%): white solid; 92% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=7.2 min, t.sub.R(minor)=9.6 min); [?].sub.D.sup.31=+3.0 (c=1.00, CHCl.sub.3); melting point: 81.4-82.4? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.26 (d, J=8.4 Hz, 2 H, ArH), 7.14 (d, J=8.0 Hz, 2 H, ArH), 2.38-2.26 (m, 5 H, CH.sub.2 and CH.sub.3), 2.17 (s, 3 H, CH.sub.3), 1.52-1.41 (m, 2 H, CH.sub.2), 1.35-1.16 (m, 8 H, 4 x CH.sub.2), 0.85 (t, J=6.8 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.9, 137.4, 132.0, 129.2, 126.0, 105.1, 101.6, 31.8, 29.14, 29.07, 28.6, 28.1, 22.6, 21.1, 16.3, 14.0; IR (neat): ?=2955, 2926, 2856, 1941, 1681, 1417, 1278, 1063 cm.sup.?1; MS (70 eV, EI) m/z (%): 287 (M.sup.++1, 2.80), 286 (M.sup.+, 6.61), 157 (100); Anal. Calcd. for C.sub.19H.sub.26O.sub.2: C 79.68, H 9.15; found C 79.78, H 9.18.
EXAMPLE 24
[0119] ##STR00062##
[0120] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0147 g, 0.0012 mmol), (S)-CPA-1 (0.0081 g, 0.01 mmol), (?)-1x (0.0585 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2x (0.0495 g, 77%): white solid; 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=6.4 min, t.sub.R(minor)=9.7 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.30 (s, 4 H, ArH), 2.31 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.17 (s, 3 H, CH.sub.3), 1.51-1.39 (m, 2 H, CH.sub.2), 1.34-1.17 (m, 10 H, 5 x CH.sub.2), 0.86 (t, J=6.8 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.5, 133.6, 133.4, 128.7, 127.3, 104.4, 102.2, 31.8, 29.3, 29.2, 29.1, 28.5, 28.0, 22.6, 16.3, 14.0.
EXAMPLE 25
[0121] ##STR00063##
[0122] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0036 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.037 g, 0.03 mmol), (S)-CPA-1 (0.02 g, 0.025 mmol), (?)-1y (0.211 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1) to afford a product: chiral allenoic acid (S)-2y (0.1459 g, 65%): white solid; 92% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 0.5 mL/min, ?=214 nm, t.sub.R(major)=10.2 min, t.sub.R(minor)=14.5 min); [?].sub.D.sup.25=?3.4 (c=1.04, CHCl.sub.3); melting point: 81.1-81.6? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.45 (d, J=8.4 Hz, 2 H, ArH), 7.23 (d, J=8.4 Hz, 2 H, ArH), 2.31 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.16 (s, 3 H, CH.sub.3), 1.51-1.39 (m, 2 H, CH.sub.2), 1.36-1.12 (m, 22 H, 11 x CH.sub.2), 0.88 (t, J=6.6 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.7, 134.1, 131.6, 127.6, 121.5, 104.5, 102.2, 31.9, 29.68, 29.66, 29.64, 29.59, 29.4, 29.3, 29.2, 28.5, 28.0, 22.7, 16.2, 14.1; IR (neat): ?=2921, 2854, 1940, 1685, 1475, 1417, 1271, 1079, 1017 cm.sup.?1; MS (70 eV, EI) m/z (%): 450 (M.sup.+ (.sup.81Br), 4.83), 448 (M.sup.+ (.sup.79Br), 4.76), 143 (100); Anal. Calcd. for C.sub.25H.sub.37BrO.sub.2: C 66.81, H 8.30; found C 66.84, H 8.21.
EXAMPLE 26
[0123] ##STR00064##
[0124] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0149 g, 0.0012 mmol), (S)-CPA-1 (0.004 g, 0.005 mmol), (?)-1z (0.0503 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), Toluene (0.8 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2z (0.0455 g, 81%): white solid; 92% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=14.3 min, t.sub.R(minor)=25.7 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.34-7.21 (m, 7 H, ArH), 7.19-7.13 (m, 3 H, ArH), 2.84 (t, J=7.6 Hz, 2 H, CH.sub.3), 2.75-2.59 (m, 2 H, CH.sub.2), 2.02 (s, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.9, 172.6, 141.1, 134.7, 128.5, 128.3, 127.6, 126.1, 125.9, 105.5, 100.7, 34.0, 30.3, 16.1.
EXAMPLE 27
[0125] ##STR00065##
[0126] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0148 g, 0.0012 mmol), (S)-CPA-1 (0.0081 g, 0.01 mmol), (?)-1aa (0.0475 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 65? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2aa (0.0328 g, 62%): white solid; 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=16.8 min, t.sub.R(minor)=25.0 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.42-7.31 (m, 4 H, ArH), 7.29-7.24 (m, 1 H, ArH), 3.50 (t, J=6.6 Hz, 2 H, CH.sub.2), 2.36 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.20 (s, 3 H, CH.sub.3), 1.84-1.76 (m, 2 H, CH.sub.2), 1.69-1.57 (m, 2 H, CH.sub.2); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.6, 134.7, 128.6, 127.7, 126.1, 105.7, 101.1, 44.6, 32.0, 27.8, 25.3, 16.4.
EXAMPLE 28
[0127] ##STR00066##
[0128] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0073 g, 0.02 mmol), chiral bisphosphine ligand (S)-L4d (0.0733 g, 0.06 mmol), (S)-CPA-1 (0.01 g, 0.0125 mmol), (?)-1ab (0.1069 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.786 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate/dichloromethane=10/1/1, then petroleum ether (60?90? C.)/ethyl acetate=3/1) to afford a product: chiral allenoic acid (S)-2ab (0.0328 g, 62%): white solid; 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=16.8 min, t.sub.R(minor)=25.0 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.42-7.31 (m, 4 H, ArH), 7.29-7.24 (m, 1 H, ArH), 3.50 (t, J=6.6 Hz, 2 H, CH.sub.2), 2.36 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.20 (s, 3 H, CH.sub.3), 1.84-1.76 (m, 2 H, CH.sub.2), 1.69-1.57 (m, 2 H, CH.sub.2); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.6, 134.7, 128.6, 127.7, 126.1, 105.7, 101.1, 44.6, 32.0, 27.8, 25.3, 16.4.
EXAMPLE 29
[0129] ##STR00067##
[0130] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0038 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0368 g, 0.03 mmol), (S)-CPA-1 (0.01 g, 0.0125 mmol), (?)-1ac (0.1775 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 65? C. for 10 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ether/dichloromethane=10/1/1, then petroleum ether (60?90? C.)/ethyl acetate=8/1) to afford a product: chiral allenoic acid (S)-2ac (0.1166 g, 61%): white solid; 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=90/10, 1.0 mL/min, ?=214 nm, t.sub.R(major)=6.8 min, t.sub.R(minor)=8.2 min); [?].sub.D.sup.25=?31.4 (c=1.00, CHCl.sub.3); melting point: 171.1-172.2? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=8.07 (d, J=7.6 Hz, 2 H, ArH), 7.43-7.23 (m, 9 H, ArH), 7.19 (t, J=7.4 Hz, 2 H, ArH), 4.30 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.46 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.20 (s, 3 H, CH.sub.3), 2.12-1.98 (m, 2 H, CH.sub.2); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.2, 172.1, 140.3, 134.6, 128.7, 127.9, 126.1, 125.6, 122.8, 120.3, 118.8, 108.5, 106.3, 100.9, 42.6, 27.2, 26.3, 16.5; IR (neat): ?=3054, 2936, 1940, 1682, 1454, 1335, 1262, 1021 cm.sup.?1; MS (70 eV, EI) m/z (%): 382 (M.sup.++1, 7.06), 381 (M.sup.+, 20.11), 193 (100); Anal. Calcd. for C26H23NO2: C 81.86, H 6.08; found C 81.97, H 6.07.
EXAMPLE 30
[0131] ##STR00068##
[0132] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0035 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0368 g, 0.03 mmol), (S)-CPA-1 (0.0101 g, 0.0125 mmol), (?)-1ad (0.1234 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate/dichloromethane=10/1/1, then petroleum ether (60?90? C.)/ethyl acetate=8/1) to afford a product: chiral allenoic acid (S)-2ad (0.1134 g, 83%): oil substance; 91% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=90/10, 1.0 mL/min, ?=214 nm, t.sub.R(major)=7.8 min, t.sub.R(minor)=10.8 min); [?].sub.D.sup.27=+7.5 (c=1.00, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.45-7.29 (m, 4 H, ArH), 7.29-7.24 (m, 1 H, ArH), 4.09 (t, J=6.4 Hz, 2 H, CH.sub.2), 2.42 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.21 (s, 3 H, CH.sub.3), 2.02 (s, 3 H, CH.sub.3), 1.88-1.76 (m, 2 H, CH.sub.2); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.3, 172.3, 171.2, 134.6, 128.6, 127.7, 126.0, 105.8, 100.8, 63.7, 27.0, 25.2, 20.8, 16.3; IR (neat): ?=2956, 2929, 1942, 1737, 1717, 1681, 1367, 1238, 1041 cm.sup.?1; MS (70 eV, ESI) m/z: 297 (M+Na.sup.+), 275 (M+H.sup.+); HRMS calcd for C.sub.16H.sub.19O.sub.4 [M+H.sup.+]: 275.1278, found: 275.1271.
EXAMPLE 31
[0133] ##STR00069##
[0134] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (S)-L4d (0.0149 g, 0.0012 mmol), (S)-CPA-1 (0.0041 g, 0.005 mmol), (?)-1ae (0.0347 g, 0.2 mmol), bromobenzene (211 ?L, d=1.49 g/mL, 0.3144 g, 2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 65? C. for 15 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2ae (0.0237 g, 55%): white solid; 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=16.8 min, t.sub.R(minor)=25.0 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.42-7.31 (m, 4 H, ArH), 7.29-7.24 (m, 1 H, ArH), 3.50 (t, J=6.6 Hz, 2 H, CH.sub.2), 2.36 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.20 (s, 3 H, CH.sub.3), 1.84-1.76 (m, 2 H, CH.sub.2), 1.69-1.57 (m, 2 H, CH.sub.2); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.6, 134.7, 128.6, 127.7, 126.1, 105.7, 101.1, 44.6, 32.0, 27.8, 25.3, 16.4.
EXAMPLE 32
[0135] ##STR00070##
[0136] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0037 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0368 g, 0.03 mmol), (S)-CPA-1 (0.0101 g, 0.0125 mmol), (?)-1af (0.142 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 15/1) to afford a product: chiral allenoic acid (S)-2af (0.0904 g, 59%): white solid; 92% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 0.5 mL/min, ?=214 nm, t.sub.R(major)=13.1 min, t.sub.R(minor)=16.7 min); [?].sub.D.sup.25=?5.4 (c=1.00, CHCl.sub.3); melting point: (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.44-7.34 (m, 4 H, ArH), 7.32-7.27 (m, 1 H, ArH), 2.47 (td, J.sub.1=7.5 Hz, J.sub.2=2.0 Hz, 2 H, CH.sub.2), 2.29 (t, J=7.2 Hz, 2 H, CH.sub.2), 2.24 (s, 3 H, CH.sub.3), 1.80-1.70 (m, 2 H, CH.sub.2), 0.15 (s, 9 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.6, 172.6, 134.8, 128.6, 127.7, 126.1, 106.6, 105.6, 100.9, 84.9, 27.8, 26.9, 19.3, 16.4, 0.1; IR (neat): ?=2958, 2173, 1941, 1682, 1417, 1281, 1250, 1026 cm.sup.?1; MS (70 eV, ESI) m/z: 313 (M+H.sup.+); Anal. Calcd. for C.sub.19H.sub.24O.sub.2Si: C 73.03, H 7.74; found C 73.19, H 7.75.
EXAMPLE 33
[0137] ##STR00071##
[0138] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0038 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0369 g, 0.03 mmol), (S)-CPA-1 (0.0102 g, 0.0125 mmol), (?)-1af (0.1421 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 15/1) to afford a product: chiral allenoic acid (R)-2af (0.0965 g, 62%): white solid; 92% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 0.5 mL/min, ?=214 nm, t.sub.R(minor)=13.3 min, t.sub.R(major)=16.0 min); [?].sub.D.sup.25=+5.5 (c=1.00, CHCl.sub.3); melting point: 97.2-98.5? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.45-7.33 (m, 4 H, ArH), 7.33-7.26 (m, 1 H, ArH), 2.47 (td, J.sub.1=7.5 Hz, J.sub.2=2.3 Hz, 2 H, CH.sub.2), 2.29 (t, J=7.0 Hz, 2 H, CH.sub.2), 2.24 (s, 3 H, CH.sub.3), 1.81-1.70 (m, 2 H, CH.sub.2), 0.15 (s, 9 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.6, 172.6, 134.8, 128.6, 127.7, 126.1, 106.6, 105.6, 100.9, 84.9, 27.8, 26.9, 19.3, 16.4, 0.1; IR (neat): ?=2957, 2173, 1941, 1681, 1416, 1281, 1249, 1026 cm.sup.?1; MS (70 eV, ESI) m/z: 335 (M+Nat), 313 (M+H.sup.+); Anal. Calcd. for C.sub.19H.sub.24O.sub.2Si: C 73.03, H 7.74; found C 73.26, H 8.01.
EXAMPLE 34
[0139] ##STR00072##
[0140] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0074 g, 0.02 mmol), chiral bisphosphine ligand (S)-L4d (0.0763 g, 0.06 mmol), (S)-CPA-1 (0.02 g, 0.025 mmol)), (?)-1ag (0.1085 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 15/1) to afford a product: chiral allenoic acid (S)-2ag (0.0975 g, 80%): white solid; 89% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=7.4 min, t.sub.R(minor)=9.1 min); [?].sub.D.sup.25=+12.3 (c=1.00, CHCl.sub.3); melting point: 64.4-65.4? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.38 (d, J=7.2 Hz, 2 H, ArH), 7.33 (t, J=7.8 Hz, 2 H, ArH), 7.27-7.21 (m, 1 H, ArH), 2.55 (quartet, J=7.3 Hz, 2 H, CH.sub.2), 2.33 (t, J=7.6 Hz, 2 H, CH.sub.2), 1.52-1.41 (m, 2 H, CH.sub.2), 1.41-1.29 (m, 2 H, CH.sub.2), 1.17 (t, J=7.4 Hz, 3 H, CH.sub.3), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.2, 173.3, 134.9, 128.6, 127.5, 126.3, 112.1, 103.8, 30.4, 28.4, 23.2, 22.4, 13.8, 12.3; IR (neat): ?=2960, 2931, 2873, 1939, 1678, 1415, 1277 cm.sup.?1; MS (70 eV, EI) m/z (%): 245 (M.sup.++1, 1.08), 244 (M.sup.+, 5.31), 129 (100); Anal. Calcd. for C.sub.16H.sub.20O.sub.2: C 78.65, H 8.25; found C 78.73, H 8.40.
EXAMPLE 35
[0141] ##STR00073##
[0142] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0075 g, 0.02 mmol), chiral bisphosphine ligand (S)-L4d (0.0735 g, 0.06 mmol), (S)-CPA-1 (0.0302 g, 0.0375 mmol), (?)-1ag (0.1152 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 15/1) to afford a product: chiral allenoic acid (S)-2ag (0.1025 g, 79%): white solid; 77% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=7.2 min, t.sub.R(minor)=9.1 min); [?].sub.D.sup.26=+12.7 (c=1.02, CHCl.sub.3); melting point: 62.9-64.0? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.38 (d, J=6.8 Hz, 2 H, ArH), 7.33 (t, J=8.0 Hz, 2 H, ArH), 7.28-7.21 (m, 1 H, ArH), 2.51 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.32 (t, J=7.6 Hz, 2 H, CH.sub.2), 1.64-1.51 (m, 2H, CH.sub.2), 1.51-1.40 (m, 2 H, CH.sub.2), 1.40-1.29 (m, 2 H, CH.sub.2), 1.01 (t, J=7.4 Hz, 3 H, CH.sub.3), 0.87 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.4, 173.2, 134.9, 128.6, 127.5, 126.4, 110.3, 102.9, 32.2, 30.4, 28.4, 22.4, 21.0, 13.9, 13.8; IR (neat): ?=2957, 2929, 2872, 1938, 1676, 1494, 1453, 1276 cm.sup.?1; MS (70 eV, EI) m/z (%): 258 (M.sup.+, 6.49), 129 (100); Anal. Calcd. for C.sub.17H.sub.22O.sub.2: C 79.03, H 8.58; found C 79.26, H 9.12.
EXAMPLE 36
[0143] ##STR00074##
[0144] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0036 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0367 g, 0.03 mmol), (S)-CPA-1 (0.0502 g, 0.0625 mmol)), 5 (0.192 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid 10 (0.1492 g, 72%): oil substance; >20:1 dr; [?].sub.D.sup.24=?37.7 (c=1.54, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=8.02 (d, J=8.4 Hz, 2 H, ArH), 7.44 (d, J =8.4 Hz, 2 H, ArH), 4.92 (td, J.sub.1=11.0 Hz, J.sub.2=4.4 Hz, 1 H, CH), 2.34 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.21 (s, 3 H, CH.sub.3), 2.17-2.09 (m, 1 H, CH), 2.02-1.86 (m, 1 H, CH), 1.73 (d, J=11.2 Hz, 2 H, CH.sub.2), 1.64-1.50 (m, 2 H, CH.sub.2), 1.50-1.40 (m, 2 H, CH.sub.2), 1.40-1.30 (m, 2 H, CH.sub.2), 1.20-1.02 (m, 2 H, CH.sub.2), 1.00-0.84 (m, 10 H, CH and 3 x CH.sub.3), 0.79 (d, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=213.1, 172.3, 165.8, 139.7, 129.81, 129.76, 125.9, 104.8, 102.3, 74.9, 47.3, 40.9, 34.3, 31.4, 30.2, 28.2, 26.6, 23.7, 22.2, 22.0, 20.7, 16.6, 16.2, 13.8; IR (neat): ?=2956, 2928, 2868, 1941, 1709, 1683, 1271, 1112 cm.sup.?1; MS (70 eV, ESI) m/z: 435 (M+Na.sup.+); HRMS calcd for C.sub.26H.sub.36O.sub.4Na [M+Na.sup.+]: 435.2506, found: 435.2501.
EXAMPLE 37
[0145] ##STR00075##
[0146] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0037 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0368 g, 0.03 mmol), (S)-CPA-1 (0.0504 g, 0.0625 mmol)), 6 (0.1902 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid 11 (0.1445 g, 71%): oil substance; >20:1 dr; [?].sub.D.sup.25=?22.3 (c=1.00, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=8.03 (d, J=8.4 Hz, 2 H, ArH), 7.44 (d, J=8.4 Hz, 2 H, ArH), 5.84 (s, 1 H, ?CH), 4.95-4.43 (m, 4 H, ?CH.sub.2 and CH.sub.2), 2.34 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.28-2.07 (m, 7 H, 2 x CH.sub.2 and CH.sub.3), 2.05-1.96 (m, 1 H, one proton of CH.sub.2), 1.91-1.82 (m, 1 H, one proton of CH.sub.2), 1.75 (s, 3 H, CH.sub.3), 1.58-1.40 (m, 3 H, CH and CH.sub.2), 1.39-1.29 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=213.1, 172.2, 166.2, 149.5, 139.9, 132.6, 129.9, 129.3, 125.9, 125.6, 108.8, 104.8, 102.3, 68.8, 40.8, 30.4, 30.1, 28.2, 27.3, 26.4, 22.2, 20.7, 16.2, 13.8; IR (neat): ?=2957, 2925, 2863, 1941, 1716, 1683, 1415, 1268, 1104 cm.sup.?1; MS (70 eV, EI) m/z (%): 409 (M.sup.++1, 1.37), 408 (M.sup.+, 4.44), 257 (100); HRMS calcd for C.sub.26H.sub.32O.sub.4 [M.sup.+]: 408.2301, found: 408.2299.
EXAMPLE 38
[0147] ##STR00076##
[0148] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0037 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0367 g, 0.03 mmol), (S)-CPA-1 (0.0506 g, 0.0625 mmol), 7 (0.1922 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid 12 (0.1488 g, 72%): oil substance; >20:1 dr; [?].sub.D.sup.25=+11.2 (c=1.00, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=8.01 (d, J=8.0 Hz, 2 H, ArH), 7.44 (d, J=8.4 Hz, 2 H, ArH), 5.10 (t, J=6.8 Hz, 1 H, ?CH), 4.45-4.23 (m, 2 H, CH.sub.2), 2.34 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.21 (s, 3 H, CH.sub.3), 2.09-1.92 (m, 2 H, CH.sub.2), 1.86-1.77 (m, 1 H, CH), 1.72-1.52 (m, 8 H, CH.sub.2 and 2 x CH.sub.3), 1.50-1.21 (m, 6 H, 3 x CH.sub.2), 0.97 (d, J=6.8 Hz, 3 H, CH.sub.3), 0.88 (t, J=7.4 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=213.1, 172.3, 166.4, 139.8, 131.3, 129.8, 129.4, 125.9, 124.5, 104.8, 102.3, 63.5, 36.9, 35.4, 30.1, 29.6, 28.2, 25.7, 25.4, 22.2, 19.5, 17.6, 16.2, 13.8; IR (neat): ?=2959, 2923, 2864, 1941, 1717, 1683, 1457, 1271, 1108 cm.sup.?1; MS (70 eV, EI) m/z (%): 412 (M.sup.+, 2.99), 81 (100); HRMS calcd for C.sub.26H.sub.36O.sub.4 [M.sup.+]: 412.2614, found: 412.2609.
EXAMPLE 39
[0149] ##STR00077##
[0150] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0038 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0368 g, 0.03 mmol), (S)-CPA-1 (0.06 g, 0.0625 mmol)), 8 (0.3078 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a crude product: chiral allenoic acid S1-13 (0.2963 g), all of which was put to the next reaction.
[0151] S1-13 (0.2963 g, ?0.5 mmol), NBS (N-bromosuccinimide) (0.1064 g, 0.6 mmol) and CHCl.sub.3 (5 mL) were added in sequence to a dry Schlenk reaction tube. The reaction tube was plugged with a rubber stopper, then reacted at room temperature for 2 hours, concentrated, and subjected to flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: bromo chiral ?-butyrolactone 13 (0.2603 g, 72%): oil substance; >20:1 dr; [?].sub.D.sup.23=+63.5 (c=1.00, CHCl.sub.3); melting point: 183.3-184.2? C. (petroleum ether/DCM); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=8.05 (d, J=8.4 Hz, 2 H, ArH), 7.45 (d, J=8.4 Hz, 2 H, ArH), 5.48-5.32 (m, 1 H, ?CH), 4.95-4.74 (m, 1 H, CH), 2.45 (d, J=7.6 Hz, 2 H, CH.sub.2), 2.36 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.06-1.67 (m, 9 H), 1.64-1.42 (m, 8 H), 1.40-1.29 (m, 5 H), 1.29-0.96 (m, 14 H), 0.95-0.89 (m, 6 H), 0.87 (dd, J.sub.1=6.8 Hz, J.sub.2=1.6 Hz, 6 H, 2 x CH.sub.3), 0.69 (s, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=170.1, 165.2, 149.8, 141.9, 139.4, 131.6, 131.3, 129.8, 125.5, 122.8, 87.7, 74.8, 56.6, 56.1, 50.0, 42.2, 39.7, 39.4, 38.1, 36.9, 36.6, 36.1, 35.7, 31.9, 31.8, 28.9, 28.2, 27.9, 27.8, 24.8, 24.2, 23.9, 23.8, 22.8, 22.5, 22.3, 21.0, 19.3, 18.7, 13.7, 11.8; IR (neat): ?=2939, 2861, 1749, 1717, 1461, 1274, 1111, 1025 cm.sup.?1; MS (DART) m/z: 740 (M(.sup.81Br)+NH.sub.4.sup.+); 738 (M(.sup.79Br)+NH.sub.4.sup.+; Anal. Calcd. for C.sub.43H.sub.61BrO.sub.4: C 71.55, H 8.52; found C 71.42, H 8.71.
EXAMPLE 40
[0152] ##STR00078##
[0153] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0037 g, 0.01 mmol), chiral bisphosphine ligand (S)-L4d (0.0364 g, 0.03 mmol), (S)-CPA-1 (0.0101 g, 0.0125 mmol)), 9 (0.2087 g, 0.5 mmol), bromobenzene (527 ?L, d=1.49 g/mL, 0.7860 g, 5 mmol), water (180 ?L, d=1.0 g/mL, 0.18 g, 10 mmol), toluene (2 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=10/1, then petroleum ether (60?90? C.)/ether/dichloromethane=4/1/1) to afford a product: chiral allenoic acid 14 (0.1379 g, 62%): oil substance; >20:1 dr; [?].sub.D.sup.21=+15.7 (c=1.10, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.70-7.54 (m, 3 H, ArH), 7.36 (dd, J.sub.1=8.6 Hz, J.sub.2=1.4 Hz, 1 H, ArH), 7.33-7.21 (m, 5 H, ArH), 7.09 (dd, J.sub.1=9.0 Hz, J.sub.2=2.6 Hz, 1 H, ArH), 7.07-7.03 (m, 1 H, ArH), 4.15-4.02 (m, 2 H, CH.sub.2), 3.90-3.75 (m, 4 H, CH and OCH.sub.3), 2.39-2.21 (m, 2 H, CH.sub.2), 2.11 (s, 3 H, CH.sub.3), 1.82-1.70 (m, 2 H, CH.sub.2), 1.54 (d, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.4, 174.6, 172.2, 157.5, 135.6, 134.6, 133.6, 129.2, 128.8, 128.5, 127.7, 127.0, 126.1, 126.0, 125.8, 118.8, 105.7, 105.5, 100.6, 63.8, 55.2, 45.3, 26.9, 25.1, 18.3, 16.2; IR (neat): ?=2938, 2850, 1941, 1725, 1682, 1454, 1265, 1182, 1029 cm.sup.?1; MS (70 eV, ESI) m/z: 467 (M+Na.sup.+); HRMS calcd for C.sub.28H.sub.28O.sub.5Na [M+Na.sup.+]: 467.1829, found: 467.1826.
EXAMPLE 41
[0154] ##STR00079##
[0155] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0368 g, 0.1 mmol), chiral bisphosphine ligand (S)-L4d (0.3638 g, 0.3 mmol), (S)-CPA-1 (0.1009 g, 0.0125 mmol), (?)-1a (1.0109 g, 5.0 mmol), bromobenzene (5.27 mL, d=1.49 g/mL, 7.8523 g, 50 mmol), water (1.8019 g, 100 mmol), toluene (20 mL) were reacted at 50? C. for 12 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=15/1, then 10/1) to afford a product: chiral allenoic acid (S)-2a (1.0227 g, 89%): white solid; 92% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.5 min, t.sub.R(minor)=11.9 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.44-7.29 (m, 4 H, ArH), 7.28-7.21 (m, 1 H, ArH), 2.32 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.19 (s, 3 H, CH.sub.3), 1.52-1.41 (m, 2 H, CH.sub.2), 1.40-1.28 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.6, 172.8, 135.0, 128.5, 127.6, 126.1, 105.2, 101.8, 30.2, 28.3, 22.2, 16.3, 13.8.
EXAMPLE 42
[0156] ##STR00080##
[0157] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0184 g, 0.1 mmol), chiral bisphosphine ligand (S)-L4d (0.1818 g, 0.3 mmol), (S)-CPA-1 (0.1007 g, 0.0125 mmol), (?)-1a (1.0115 g, 5.0 mmol), bromobenzene (5.27 mL, d=1.49 g/mL, 7.8523 g, 50 mmol), water (1.8008 g, 100 mmol), toluene (20 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 15/1) to afford a product: chiral allenoic acid (S)-2a (0.8994 g, 78%): white solid; 91% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.7 min, t.sub.R(minor)=12.3 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.43-7.28 (m, 4 H, ArH), 7.27-7.22 (m, 1 H, ArH), 2.32 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.19 (s, 3 H, CH.sub.3), 1.52-1.41 (m, 2 H, CH.sub.2), 1.40-1.28 (m, 2 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.5, 172.5, 135.0, 128.5, 127.6, 126.1, 105.2, 101.8, 30.2, 28.3, 22.3, 16.3, 13.8.
EXAMPLE 43
[0158] ##STR00081##
[0159] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0367 g, 0.1 mmol), chiral bisphosphine ligand (S)-L4d (0.3634 g, 0.3 mmol), (S)-CPA-1 (0.1008 g, 0.0125 mmol), (?)-1af (1.4219 g, 5.0 mmol), bromobenzene (5.27 mL, d=1.49 g/mL, 7.8523 g, 50 mmol), water (1.8012 g, 100 mmol), toluene (20 mL) were reacted at 50? C. for 18 hours. Flash column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1, then 15/1) to afford a product: chiral allenoic acid (R)-2af (1.1935 g, 76%): white solid; 91% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(minor)=6.7 min, t.sub.R(major)=8.1 min); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.42-7.32 (m, 4 H, ArH), 7.28-7.23 (m, 1 H, ArH), 2.43 (td, J.sub.1=7.5 Hz, J.sub.2=2.3 Hz, 2 H, CH.sub.2), 2.26 (t, J=7.0 Hz, 2 H, CH.sub.2), 2.21 (s, 3 H, CH.sub.3), 1.76-1.65 (m, 2 H, CH.sub.2), 0.12 (s, 9 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=212.6, 172.6, 134.8, 128.6, 127.7, 126.1, 106.6, 105.5, 100.9, 84.9, 27.8, 26.9, 19.3, 16.4, 0.1.
EXAMPLE 44
[0160] ##STR00082##
[0161] (S)-2a (0.4608 g, 2 mmol, 92% ee), K.sub.2CO.sub.3 (0.4152 g, 3 mmol), DMF (N,N-dimethylformamide) (10 mL) was added in sequence to a dry Schlenk reaction tube, the reaction tube was placed in a ?5? C. cold bath, and then CH.sub.3I (iodomethane) (188 ?L, d=2.28 g/mL, 0.4286 g, 3 mmol) was added, the reaction was completed after stirred in a ?5? C. cold bath for 1.5 hours as monitored by thin layer chromatography (TLC). The reaction was quenched by water (10 mL), the aqueous phase was extracted with ether (10 mL?3), the organic phases were combined, washed once with saturated ammonium chloride solution (10 mL), once with saturated brine (10 mL), separated and dried over anhydrous sodium sulfate, filtered and concentrated to afford an oily chiral allenoate which was used directly in the next reaction. All the S1 and toluene (10 mL) obtained in the previous step were added to a dry Schlenk reaction tube, the reaction tube was placed in a ?78? C. cold bath and added with DIBAL-H (diisobutylaluminum hydride) (4.2 mL, 1.0 M in Hexane, 4.2 mmol) dropwise, the reaction was completed after stirred in a ?5? C. cold bath for 4 hours as monitored by thin layer chromatography (TLC). The reaction was quenched by methanol (10 mL) at ?78? C., the reaction tube was taken out of the cold bath, and after returning to room temperature, added with water (20 mL) and 1 mol/L aqueous hydrochloric acid solution (20 mL), the aqueous phase was extracted with ether (10 mL?3), the organic phases were combined, washed once with saturated brine (10 mL), separated, and dried over anhydrous sodium sulfate, filtered, concentrated, and subjected to flash silica gel column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1) to afford chiral allenol S1-15, which is directly used in the next reaction.
[0162] All the S1-15 obtained in the previous step, Fe(NO.sub.3).sub.3.Math.9H.sub.2O (0.121 g, 0.3 mmol), 4-OH-TEMPO (0.0687 g, 0.4 mmol), NaCl (0.0236 g, 0.4 mmol), and DCE (1,2-dichloroethane) (8 mL) were added to a dry Schlenk reaction tube, the reaction was completed after stirred at room temperature for 15 hours as monitored by thin layer chromatography (TLC), and the reaction solution was filtered through a short silica gel column (3 cm), then subjected to flash column chromatography (eluent: petroleum ether (60?90? C.)/ether/dichloromethane=100/1/1) to afford a product: chiral biuronic acid 15 (0.2478 g, 58%): oil substance; 91% ee (HPLC conditions: AS-H column, hexanePPrOH=99/1, 1.0 mL/min, ?=214 nm, t.sub.R(minor)=6.5 min, t.sub.R(major)=7.6 min); [?].sub.D.sup.23=?5.1 (c=1.02, CHCl.sub.3); oil; .sup.1H NMR (400 MHz, CDCl.sub.3): ?=9.60 (s, 1 H, CHO), 7.44-7.33 (m, 4 H, ArH), 7.32-7.26 (m, 1 H, ArH), 2.31 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.26 (s, 3 H, CH.sub.3), 1.52-1.42 (m, 2 H, CH.sub.2), 1.42-1.32 (m, 2 H, CH.sub.2), 0.90 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=219.5, 192.1, 134.5, 128.7, 127.9, 125.9, 113.5, 106.6, 29.9, 24.8, 22.4, 16.6, 13.8; IR (neat): ?=2960, 2866, 1931, 1680, 1452, 1171 cm.sup.?1; MS (70 eV, EI) m/z (%): 215 (M.sup.++1, 3.12), 214 (M.sup.+, 5.61), 128 (100); HRMS calcd for C.sub.15H.sub.18O [M.sup.+]: 214.1352, found: 214.1355.
EXAMPLE 45
[0163] ##STR00083##
[0164] (S)-2a (0.1151 g, 0.5 mmol, 92% ee), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (0.1245 g, 0.65 mmol), dimethylhydroxylamine hydrochloride (0.0637 g, 0.65 mmol), 4-dimethylaminopyridine (DMAP) (0.0063 g, 0.05 mmol), triethylamine (NEt.sub.3) (90 ?L, d=0.728 g/mL, 0.0655 g, 0.65 mmol) were added to a dry Schlenk reaction tube, which was replaced with argon three times, then dichloromethane (DCM) (2 mL) was added, and the reaction was completed after stirred in a cold bath at 0? C. for 3 hours as monitored by thin layer chromatography (TLC). After diluted by Dichloromethane (5 mL), the reaction was quenched by water (5 mL), the aqueous phase was extracted with dichloromethane (5 mL?3), the organic phases were combined, washed once with saturated brine (5 mL), separated and dried over anhydrous sodium sulfate, filtered, concentrated, and subjected to flash silica gel column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=10/1) to afford a product: allenamide (S)-16 (0.1296 g, 95%): oil substance; 92% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=6.5 min, t.sub.R(minor)=7.8 min); [?].sub.D.sup.20=+125.0 (c=1.00, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.41 (d, J=8.8 Hz, 2 H, ArH), 7.34 (t, J=7.6 Hz, 2 H, ArH), 7.25-7.19 (m, 1 H, ArH), 3.51 (s, 3 H, CH.sub.3), 3.22 (s, 3 H, CH.sub.3), 2.41 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.17 (s, 3 H, CH.sub.3), 1.51-1.42 (m, 2 H, CH.sub.2), 1.42-1.31 (m, 2 H, CH.sub.2), 0.89 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=206.3, 168.1, 136.0, 128.4, 127.0, 125.8, 102.1, 101.0, 61.1, 33.9, 30.2, 30.1, 22.4, 16.5, 13.9; IR (neat): ?=2956, 2928, 2864, 1942, 1637, 1453, 1365, 1186 cm.sup.?1; MS (70 eV, ESI) m/z: 296 (M+Na.sup.+), 274 (M+H.sup.+); HRMS calcd for C.sub.17H.sub.23O.sub.2N [M+H.sup.+]: 274.1802, found: 274.1800.
EXAMPLE 46
[0165] ##STR00084##
[0166] (S)-16 (0.0545 g, 0.2 mmol, 92% ee), and tetrahydrofuran (THF) (1 mL) were added to a dry Schlenk reaction tube, which was replaced with argon three times, then the reaction tube was put in ?78? C. cold bath, and methylmagnesium bromide (0.27 mL, 3.0 M in hexane, 0.81 mmol) was added. Then the reaction was completed after stirred in a cold bath at 0? C. for 1 hour as monitored by thin layer chromatography (TLC). The reaction was quenched by saturated ammonium chloride (1 mL)at 0? C., the aqueous phase was extracted with ethyl acetate (2 mL?3), the organic phases were combined, washed once with saturated brine (3 mL), separated and dried over anhydrous sodium sulfate, filtered, concentrated, and subjected to flash silica gel column chromatography (eluent: petroleum ether (60?90? C.)/ethyl acetate=20/1) to afford a product: allenone (S)-17 (0.044 g, 97%): oil substance; 92% ee (HPLC conditions: AD-H column, hexane/.sup.iPrOH=99.5/0.5, 0.5 mL/min, ?=214 nm, t.sub.R(minor)=11.8 min, t.sub.R(major)=12.3 min); [?].sub.D.sup.21=+58.6 (c=1.01, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.45-7.31 (m, 4 H, ArH), 7.30-7.24 (m, 1 H, ArH), 2.31 (t, J=7.4 Hz, 2 H, CH.sub.2), 2.26 (s, 3 H, CH.sub.3), 2.23 (s, 3 H, CH.sub.3), 1.46-1.30 (m, 4 H, CH.sub.2), 0.88 (t, J=7.2 Hz, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=213.8, 198.9, 134.9, 128.7, 127.5, 125.7, 111.4, 104.8, 30.1, 27.2, 26.7, 22.4, 16.4, 13.8; IR (neat): ?=2955, 2925, 2860, 1931, 1676, 1454, 1358, 1234 cm.sup.?1; MS (70 eV, EI) m/z (%): 229 (M.sup.++1, 1.53), 228 (M.sup.+, 8.77), 185 (100); HRMS calcd for C.sub.16H.sub.20O [M.sup.+]: 228.1509, found: 228.1509.
EXAMPLE 47
[0167] ##STR00085##
[0168] (S)-2a (0.0462 g, 0.2 mmol, 92% ee), 18 (0.1119 g, 0.28 mmol), and PdCl.sub.2 (0.0019 g, 0.01 mmol) were added to a dry Schlenk reaction tube, which was replaced with argon three times, then TFA (trifluoroacetic acid) (12 uL, d=1.535 g/mL, 0.0184 g, 0.16 mmol) and DMA (N,N-dimethylacetamide) (2.5 mL) were added, and the reaction tube was placed in an oil bath that had been preheated to 30? C., the reaction was completed after stirred for 12 hours as monitored by thin layer chromatography (TLC). The reaction was quenched by water (2.5 mL), the aqueous phase was extracted with ether (3 mL?3), the organic phases were combined, washed once with saturated brine (5 mL), separated and dried over anhydrous sodium sulfate, filtered, concentrated, and subjected to flash silica gel column chromatography (eluent: petroleum ether (60?90? C.)/ether/dichloromethane=10/1/1) to afford a chiral cyclic product 19 (0.1009 g, 82%): Oil substance; >20:1 dr; [?].sub.D.sup.24=+81.2 (c=1.12, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.33-7.20 (m, 5 H, ArH), 5.93 (d, J=15.6 Hz, 1 H, ?CH), 5.20-4.98 (m, 2 H, 2 x ?CH), 4.36 (s, 1 H, ?CH), 3.70-3.55 (m, 1 H, CH), 2.15 (td, J.sub.1=7.8 Hz, J.sub.2=2.1 Hz, 2 H, CH.sub.2), 2.00-1.89 (m, 3 H), 1.87-1.73 (m, 7 H), 1.69-1.62 (m, 1 H), 1.61-1.45 (m, 4 H), 1.41-0.94 (m, 20 H), 0.94-0.81 (m, 10 H), 0.61 (s, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=173.4, 164.6, 138.63, 138.58, 135.4, 128.8, 128.2, 128.1, 128.0, 125.3, 116.9, 88.0, 71.7, 56.4, 56.0, 42.6, 42.0, 40.3, 40.1, 36.3, 35.7, 35.3, 35.1, 34.5, 30.4, 29.8, 29.2, 28.2, 27.1, 26.3, 24.2, 24.14, 24.09, 23.3, 22.5, 20.7, 18.3, 13.7, 11.9; IR (neat): ?=3351, 2932, 2862, 2173, 1754, 1449, 1221, 1040 cm.sup.?1; MS (70 eV, ESI) m/z: 635 (M+Na.sup.+), 613 (M+H.sup.+); HRMS calcd for C.sub.42H.sub.61O.sub.3 [M+H.sup.+]: 613.4615, found: 613.4612.
EXAMPLE 48
[0169] ##STR00086##
[0170] (R)-2af (0.6242 g, 2.0 mmol, 91% ee), CuCl (0.008 g, 0.08 mmol, weighed in a glove box) were added to a dry Schlenk reaction tube, which was replaced with argon three times, then MeOH (10 mL) was added, and the reaction tube was placed in an oil bath that had been preheated to 50? C., the reaction was completed after stirred for 30 minutes as monitored by thin layer chromatography (TLC). The resulting mixture was quickly filtered through a short silica gel column (3 cm) to remove the copper salt, eluted by 30 mL of ethyl acetate, and spin-dried to afford an oily substance, which was directly used in the next reaction. The above oil substance, K.sub.2CO.sub.3 (0.8291 g, 6 mmol) were added to a dry Schlenk reaction tube, which was replaced with argon three times, then MeOH (10 mL) was added, the reaction was completed after stirred at room temperature for 2 hours as monitored by thin layer chromatography (TLC), filtered, concentrated, and subjected to flash silica gel column chromatography (eluent: petroleum ether (60?90? C.)/ether/dichloromethane=20/1/1) to afford a chiral cyclic product (S)-20 (0.4042 g, 84%): oil substance; 91% ee (HPLC conditions: AD-H column, hexane/.sup.iPrOH=99/1, 0.9 mL/min, ?=214 nm, t.sub.R(minor)=32.5 min, t.sub.R(major)=36.4 min); [?].sub.D.sup.23=?103.3 (c=1.07, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=7.44-7.22 (m, 6 H, ArH), 2.43 (t, J=7.6 Hz, 2 H, CH.sub.2), 2.23 (td, J.sub.1=6.9 Hz, J.sub.2=2.5 Hz, 2 H, CH.sub.2), 1.97 (t, J=2.6 Hz, 1 H, CH), 1.87-1.70 (m, 5 H, CH.sub.2 and CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=172.9, 152.9, 140.0, 131.3, 128.7, 128.1, 124.7, 86.7, 83.3, 69.2, 26.8, 25.9, 24. 1, 17.9; IR (neat): ?=3294, 2933, 2116, 1750, 1444, 1261, 1036 cm.sup.?1; MS (70 eV, ESI) m/z: 263 (M+Na.sup.+), 241 (M+El+); HRMS calcd for C.sub.16H.sub.17O.sub.2 a [M+H.sup.+]: 241.1223, found: 241.1222.
EXAMPLE 49
[0171] ##STR00087##
[0172] Zidovudine (0.0681 g, 0.24 mmol), chiral cyclic product (S)-20 (0.0483 g, 0.2 mmol, 91% ee) were added to a dry Schlenk reaction tube, which replaced with argon three times, then DCM (1 mL), aqueous sodium ascorbate (0.012 g, 0.06 mmol, dissolved in 0.5 mL water), aqueous CuSO.sub.4.Math.5H.sub.2O (0.005 g, 0.02 mmol, dissolved in 0.5 mL water) were added, and the reaction was completed after stirred at room temperature for 24 hours as monitored by thin layer chromatography (TLC). After diluted by DCM (5 mL), the reaction solution was washed with saturated brine (5 mL), separated and dried over anhydrous sodium sulfate, filtered, concentrated, and subjected to flash silica gel column chromatography (eluent: ethyl acetate elution, then dichloromethane/methanol=10/1) to afford product 21 (0.0793 g, 78%): oil substance; >20:1 dr; [?].sub.D.sup.22=?62.3 (c=1.19, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3): ?=10.0-9.71 (m, 1 H, NH), 7.68-7.46 (m, 2 H, 2 x ?CH), 7.41-7.18 (m, 6 H, ?CH and ArH), 6.30 (t, J=6.4 Hz, 1 H, CH), 5.55-5.32 (m, 1 H, CH), 4.46-4.32 (m, 1 H, CH), 4.22 (br, 1 H, OH), 4.00 (d, J=11.6 Hz, 1 H, one proton of CH.sub.2), 3.81 (d, J=11.2 Hz, 1 H, one proton of CH.sub.2), 3.03-2.89 (m, 2 H, CH.sub.2), 2.75 (t, J=7.2 Hz, 2 H, CH.sub.2), 2.39-2.26 (m, 2 H, CH.sub.2), 2.01-1.89 (m, 2 H, CH.sub.2), 1.87 (s, 3 H, CH.sub.3), 1.77 (s, 3 H, CH.sub.3); .sup.13C NMR (100 MHz, CDCl.sub.3): ?=173.2, 164.3, 153.2, 150.6, 147.4, 139.8, 137.5, 131.4, 128.7, 128.1, 124.6, 121.2, 110.9, 87.1, 86.9, 85.1, 61.3, 59.1, 37.7, 26.9, 26.7, 24.8, 24.4, 12.3; IR (neat): ?=3454, 2932, 2249, 1748, 1684, 1463, 1267, 1101, 1051 cm.sup.?1; MS (70 eV, ESI) m/z: 508 (M+El+); HRMS calcd for C.sub.26H.sub.30O.sub.6N.sub.5 [M+Na.sup.+]: 508.2191, found: 508.2190.
EXAMPLE 50
[0173] ##STR00088##
[0174] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0147 g, 0.0012 mmol), organophosphoric acid 2b (0.0054 g, 0.01 mmol), (?)-1a (0.0402 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1.0 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to affored a product: chiral allenoic acid (R)-2a (NMR yield 47%): 79% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.7 min, t.sub.R(minor)=11.2 min).
EXAMPLE 51
[0175] ##STR00089##
[0176] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0147 g, 0.0012 mmol), organophosphoric acid 2b (0.0053 g, 0.01 mmol), (?)-1a (0.0399 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), fluorobenzene (1.0 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 38%): 62% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.2 min, t.sub.R(minor)=10.4 min).
EXAMPLE 52
[0177] ##STR00090##
[0178] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0014 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0148 g, 0.0012 mmol), organophosphoric acid 2b (0.0052 g, 0.01 mmol), (?)-1a (0.0402 g, 0.2 mmol), water (72 d=1.0 g/mL, 0.072 g, 4 mmol), chlorobenzene (1.0 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 42%): 68% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.3 min, t.sub.R(minor)=10.5 min).
EXAMPLE 53
[0179] ##STR00091##
[0180] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0147 g, 0.0012 mmol), organophosphoric acid 2b (0.0052 g, 0.01 mmol), (?)-1a (0.0403 g, 0.2 mmol), water (72 d=1.0 g/mL, 0.072 g, 4 mmol), bromobenzene (1.0 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 30%): 91% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.2 min, t.sub.R(minor)=10.4 min).
EXAMPLE 54
[0181] ##STR00092##
[0182] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0147 g, 0.0012 mmol), organophosphoric acid 2b (0.0051 g, 0.01 mmol), (?)-1a (0.0402 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), chloroform (1.0 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 27%): 88% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.5 min, t.sub.R(minor)=11.0 min).
EXAMPLE 55
[0183] ##STR00093##
[0184] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0146 g, 0.0012 mmol), organophosphoric acid 2a (0.0025 g, 0.01 mmol), (?)-1a (0.0402 g, 0.2 mmol), water (72 d=1.0 g/mL, 0.072 g, 4 mmol), bromobenzene (1.0 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 20%): 95% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=7.2 min, t.sub.R(minor)=10.9 min).
EXAMPLE 56
[0185] ##STR00094##
[0186] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0147 g, 0.0012 mmol), (R)-CPA-2 (0.0079 g, 0.01 mmol)), (?)-1a (0.0408 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), bromobenzene (1.0 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (S)-2a (NMR yield 0%).
EXAMPLE 57
[0187] ##STR00095##
[0188] Operations were conducted by referring to Example 1. PdCl.sub.2 (0.0008 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0148 g, 0.0012 mmol), (R)-CPA-1 (0.0077 g, 0.01 mmol), (?)-1a (0.0403 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), bromobenzene (1.0 mL), were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 23%): 93% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.8 min, t.sub.R(minor)=11.6 min).
EXAMPLE 58
[0189] ##STR00096##
[0190] Operations were conducted by referring to Example 1. [Pd(n-cinnamyl)C1]2 (0.0022 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0147 g, 0.0012 mmol), (R)-CPA-1 (0.0077 g, 0.01 mmol), (?)-1a (0.0406 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), bromobenzene (1.0 mL) were reacted at 50? C. for 6 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 69%): 83% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.6 min, t.sub.R(minor)=11.5 min).
EXAMPLE 59
[0191] ##STR00097##
[0192] Operations were conducted by referring to Example 1. Pd(PPh.sub.3)4 (0.0046 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0147 g, 0.0012 mmol), (R)-CPA-1 (0.0078 g, 0.01 mmol), (?)-1a (0.0407 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), bromobenzene (1.0 mL) were reacted at 50? C. for 6 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 16%): 82% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.3 min, t.sub.R(minor)=11.0 min).
EXAMPLE 60
[0193] ##STR00098##
[0194] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4a (0.0078 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), (?)-1a (0.0402 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1.0 mL), were reacted at 50? C. for 12 hours. NMR monitored that the reaction hardly occurs.
EXAMPLE 61
[0195] ##STR00099##
[0196] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4b (0.0087 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), (?)-1a (0.0405 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1.0 mL) were reacted at 50? C. for 12 hours. NMR monitored that the reaction did not occur.
EXAMPLE 62
[0197] ##STR00100##
[0198] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4f (0.0151 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), (?)-1a (0.0404 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1.0 mL), were reacted at 50? C. for 12 hours. NMR monitored that the reaction did not occur.
EXAMPLE 63
[0199] ##STR00101##
[0200] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0146 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), dppe (0.0049 g, 0.012 mmol), (?)-1a (0.0403 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1.0 mL) were reacted at 50? C. for 12 hours. NMR monitored that the reaction did not occur.
EXAMPLE 64
[0201] ##STR00102##
[0202] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0145 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), PPh.sub.3 (0.0053 g, 0.01 mmol), (?)-1a (0.0401 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1.0 mL) were reacted at 50? C. for 12 hours. NMR monitored that the reaction did not occur.
EXAMPLE 65
[0203] ##STR00103##
[0204] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0014 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0146 g, 0.0012 mmol), (R)-CPA-1 (0.0041 g, 0.005 mmol)), P(4-MeOC.sub.6H.sub.4).sub.3 (0.0069 g, 0.01 mmol), (?)-1a (0.0401 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (1.0 mL) were reacted at 50? C. for 12 hours. NMR monitored that the reaction did not occur.
EXAMPLE 66
[0205] ##STR00104##
[0206] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0144 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), P(4-CH.sub.3OC.sub.6H.sub.4).sub.3 (0.0094 g, 0.01 mmol), (?)-1a (0.0398 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol)), toluene (1.0 mL) reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 50%): 75% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.9 min, t.sub.R(minor)=12.4 min).
EXAMPLE 67
[0207] ##STR00105##
[0208] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0145 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), CH.sub.2Cl.sub.2 (128 ?L, d=1.32 g/mL, 0.1698 g, 2 mmol), (?)-1a (0.0400 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.88 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 57%): 72% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=8.9 min, t.sub.R(minor)=12.1 min).
EXAMPLE 68
[0209] ##STR00106##
[0210] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0146 g, 0.0012 mmol), (R)-CPA-1 (0.0041 g, 0.005 mmol), CHCl.sub.3 (161 ?L, d=1.48 g/mL, 0.2388 g, 2 mmol), (?)-1a (0.0399 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.84 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 66%): 87% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.0 min, t.sub.R(minor)=12.3 min).
EXAMPLE 69
[0211] ##STR00107##
[0212] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0146 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol)), CCl.sub.4 (193 ?L, d=1.02 g/mL, 0.3076 g, 2 mmol), (?)-1a (0.0401 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.81 mL) were reacted at 50? C. for 12 hours. NMR monitored that the reaction did not occur.
EXAMPLE 70
[0213] ##STR00108##
[0214] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0014 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0146 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), CHBr.sub.3 (174 ?L, d=2.89 g/mL, 0.502 g, 2 mmol), (?)-1a (0.0401 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.83 mL) were reacted at 50? C. for 12 hours. NMR monitored that the reaction did not occur.
EXAMPLE 71
[0215] ##STR00109##
[0216] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0145 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), .sup.nBuBr (214 ?L, d=1.28 g/mL, 0.274 g, 2 mmol), (?)-1a (0.0400 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.8 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 66%): 77% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.0 min, t.sub.R(minor)=12.6 min).
EXAMPLE 72
[0217] ##STR00110##
[0218] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0145 g, 0.0012 mmol), (R)-CPA-1 (0.0041 g, 0.005 mmol), PhF (188 ?L, d=1.02 g/mL, 0.1922 g, 2 mmol), (?)-1a (0.0403 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.81 mL) were reacted at 50? C. for 12 hours, purifiec by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 68%): 68% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.3 min, t.sub.R(minor)=13.2 min).
EXAMPLE 73
[0219] ##STR00111##
[0220] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0147 g, 0.0012 mmol), (R)-CPA-1 (0.0041 g, 0.005 mmol), PhCl (220 ?L, d=1.02 g/mL, 0.2252 g, 2 mmol), (?)-1a (0.0400 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.78 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 72%): 82% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.3 min, t.sub.R(minor)=12.8 min).
EXAMPLE 74
[0221] ##STR00112##
[0222] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0145 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), (4-MeOC.sub.6H.sub.4)Br (250 ?L, d=1.49 g/mL, 0.374 g, 2 mmol), (?)-1a (0.0405 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.75 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 83%): 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.3 min, t.sub.R(minor)=13.4 min).
EXAMPLE 75
[0223] ##STR00113##
[0224] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0016 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0146 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), (4-MeC.sub.6H.sub.4)Br (220 ?L, d=1.55 g/mL, 0.342 g, 2 mmol), (?)-1a (0.0405 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL), 0.072 g, 4 mmol), toluene (0.78 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid (R)-2a (NMR yield 85%): 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.4 min, t.sub.R(minor)=13.5 min).
EXAMPLE 76
[0225] ##STR00114##
[0226] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0148 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol), (4-FC.sub.6H.sub.4)Br (220 ?L, d=1.59 g/mL, 0.350 g, 2 mmol), (?)-1a (0.0405 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL), 0.072 g, 4 mmol), toluene (0.78 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid product (R)-2a (NMR yield 85%): 90% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t R t.sub.R(major)=9.3 min, t.sub.R(minor)=13.4 min).
EXAMPLE 77
[0227] ##STR00115##
[0228] Operations were conducted by referring to Example 1. [Pd(?-allyl)Cl].sub.2 (0.0015 g, 0.004 mmol), chiral bisphosphine ligand (R)-L4d (0.0146 g, 0.0012 mmol), (R)-CPA-1 (0.0040 g, 0.005 mmol)), (4-CF.sub.3C.sub.6H.sub.4)Br (280 ?L, d=1.61 g/mL, 0.450 g, 2 mmol), (?)-1a (0.0401 g, 0.2 mmol), water (72 ?L, d=1.0 g/mL, 0.072 g, 4 mmol), toluene (0.78 mL) were reacted at 50? C. for 12 hours, purified by preparative plate chromatography (developing solvent: petroleum ether (60?90? C.)/ethyl acetate=5/1) to afford a product: chiral allenoic acid product (R)-2a (NMR yield: 78%): 91% ee (HPLC conditions: AS-H column, hexane/.sup.iPrOH=98/2, 1.0 mL/min, ?=214 nm, t.sub.R(major)=9.3 min, t.sub.R(minor)=13.5 min).
[0229] 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.