CN109503656B - Novel method for efficiently preparing R-/S-diaryl methyl substituted chiral organic phosphonate through chiral induction - Google Patents
Novel method for efficiently preparing R-/S-diaryl methyl substituted chiral organic phosphonate through chiral induction Download PDFInfo
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
- C07F9/32—Esters thereof
- C07F9/3258—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3276—Esters with cycloaliphatic alcohols
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3241—Esters of arylalkanephosphinic acids
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Abstract
The invention provides a method for efficiently and selectively synthesizing chiral R-/S-diaryl methyl substituted chiral organic phosphonate derivatives containing different substituted functional groups, which adopts cesium carbonate as a catalyst and takes a chiral P- (O) -H compound and a 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound as reaction substrates. The reaction system is added with an organic solvent. The method has the advantages that: the catalyst is cheap and easy to obtain; the substrate applicability is high; the reaction condition is mild, safe and reliable; the stereoselectivity of the obtained target product is more than 99 percent, and the yield is as high as more than 80 percent. The method overcomes the defects of poor reaction enantioselectivity, complicated reaction steps and the like of the traditional synthesis of chiral R-/S-diaryl methyl substituted chiral organic phosphonate derivatives, avoids the traditional chiral resolution method, and has good industrial application prospect. The invention also provides corresponding chiral R-/S-diarylmethyl substituted chiral organic phosphonate derivatives containing different substituted functional groups.
Description
Technical Field
The invention relates to the field of application catalytic synthesis of chiral organic phosphonate compounds, in particular to a preparation method for preparing R-/S-diaryl methyl-substituted chiral organic phosphonate derivatives by carrying out 1, 6-addition reaction on a chiral P (O) -H compound and a 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound with high stereoselectivity.
Background
R-/S-diarylmethyl substituted chiral organic phosphonate is an important organic intermediate. They have wide application in the preparation of chiral drugs, anti-cancer preparations, efficient flame retardants, chiral catalyst ligands and the like. Among various organophosphorus compounds having different coordination, the studies of mono-, di-and hexa-coordination compounds have been recently conducted, and their processes as organic synthesis building blocks have not yet been developed. At present, organophosphorus reagents are mainly limited to tri-, tetra-and penta-coordinate phosphorus compounds, and particularly, tri-tetra-coordinate compounds have wide application in organic synthesis or phosphate functionalized modification.
The penta-coordinate phosphorus reagent is eventually converted to a tetra-coordinate phosphorus compound during the phosphorylation reaction, especially a tetra-coordinate phosphorus compound containing a high-functional phosphoryl group (P = O). The phosphorus reagent of three four coordination, mainly four coordination, in the reaction process, often uses phosphorus pentacoordinate compound as intermediate or transition state, just because of the mutual transformation between the compounds with different coordination numbers, the organophosphorus reagent is widely used in organic synthesis, becomes the important component of organic phosphorus chemistry, especially organic synthesis chemistry.
The method for synthesizing diarylmethyl substituted organic phosphonate ester reported in literature mainly comprises the following steps: (1)Friedel-Craftsreaction: carrying out coupling reaction on a compound containing P (O) -H or P (O) -X and a compound containing 1, 1-diaryl substituted alcohol (hydrocarbon) under the catalysis of ferric trichloride; (2) nucleophilic coupling reaction: catalyzing the cross coupling reaction of the P (O) -H compound and the 1, 1-diaryl substituted halogenated hydrocarbon by adopting the P (O) -H compound in the presence of reagents such as transition metal (iron, copper, nickel, palladium and the like) and alkali; (3) and (3) arylation reaction: the alpha-benzyl substituted organic phosphonate compound and halogenated aromatic hydrocarbon are used for cross coupling reaction under the catalysis of transition metal; (4) 1, 6-addition reaction: the P (O) -H compound and the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-ketone compound are utilized to carry out corresponding 1, 6-addition reaction under the catalysis of a carbene special ligand or a transition metal: performing cross coupling reaction on a P (O) -OR compound and nucleophilic reagent alcohol under the condition of angiotensin catalysis; (5) arbuzov reaction: utilizing trialkyl phosphites as nucleophilesThe reagent reacts with alkyl halide to prepare diaryl methyl substituted organic phosphate. However, it is currently aboutR-/SMethods for synthesizing diarylmethyl-substituted chiral organic phosphonate compounds have not been reported, and the methods generally employ air-sensitive reagents (P (OR))3Compounds, phosphorus oxychloride and the like), special ligands (ferrocene ligands, carbene ligands and the like) and transition metal catalysts (iron, copper, nickel, palladium and the like), and has the defects of complicated experimental steps, expensive catalysts, difficulty in recycling, harsh reaction conditions, cross-reactivity of substrates, low yield, great pollution to the environment and the like.
To date, compriseR-/SThe efficient synthesis of diaryl methyl substituted chiral organic phosphonate compounds has the problems of raw material quality, production safety (trialkyl phosphite, phosphorus oxychloride and other compounds have strong corrosivity), large chiral resolution difficulty, product stability, product purity and the like, the synthesis technology has high difficulty, only several companies in the countries of America, Japan and the like are producing at present, and the current situation of high-end chiral organic phosphonate products in China mainly depends on import.
Aiming at the defects of the existing chiral organic phosphonate synthesis process, the industry is focusing on the research and development of the corresponding content of the chiral P (O) -H compound which is stable, cheap and easy to obtain and is used as a phosphorylation reagent by utilizing the efficient catalysis of a cheap catalystR-/SA novel method for substituting chiral organic phosphonate compounds by diarylmethyl.
Disclosure of Invention
The invention aims to provide a novel method for inducing the formation of chiral quaternary carbon by using a cheap and easily-obtained chiral P (O) -H compound and a 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound as raw materials to perform 1, 6-addition reaction and utilizing a phosphorus chiral center to realize high stereoselectivity, so as to overcome the defects in the prior art.
The invention aims to provide a method for synthesizing corresponding chiral P (O) -H compound and 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-ketone compound with high stereoselectivityR-/SThe novel method for substituting chiral organic phosphonate compounds by diarylmethyl has the following specific reaction formula:
the method is characterized by comprising the following steps:
taking a chiral P (O) -H compound, 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one, a catalyst and an organic solvent with reaction amount, placing the mixture in a reaction vessel under the condition of nitrogen, mixing, and reacting for 6-12 hours at 25-100 ℃ under stirring to obtain corresponding compounds containing different substituted functional groupsR-/S-diarylmethyl substituted chiral organophosphonate derivatives. To produceR-/SThe diaryl methyl substituted chiral organic phosphonate ester compounds (A and B) can be separated and purified by a column chromatography (eluent: petroleum ether: ethyl acetate = 2: 1-5: 1);
wherein the content of the first and second substances,
R1is phenyl, 2,4, 6-trimethylphenyl, benzyl;
R2is a menthol group;
ar is phenyl, 4-bromophenyl, 4-benzyloxyphenyl, 4-methylphenyl, 4-tert-butylphenyl.
The chiral P (O) -H compound and the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound are synthesized into the compound with high stereoselectivityR-/SIn the method for substituting the chiral organic phosphonate compound by the diarylmethyl, the chiral P (O) -H compound is selected from (A), (B), (CRp-phenylphosphonic acid menthyl ester, (iii) p-phenylphosphonic acid menthyl esterRp-menthyl 2,4, 6-trimethylphenylphosphonate,(s) ((s))Rp) -benzyl phosphonate menthyl ester.
The chiral P (O) -H compound and the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound are synthesized into the compound with high stereoselectivityR-/SIn the method for substituting chiral organic phosphonate compounds by diarylmethyl, the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-ketone compound is selected from 4-phenylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 4- (4-bromophenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 4- (4-benzyloxyphenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 4- (4-methylphenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 4- (4-tert-butylphenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one.
The chiral P (O) -H compound and the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound are synthesized into the compound with high stereoselectivityR-/SIn the method for substituting the chiral organic phosphonate compound by the diarylmethyl, the organic solvent is dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, methanol, dioxane, toluene,N, N-dimethylformamide.
The chiral P (O) -H compound and the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound are synthesized into the compound with high stereoselectivityR-/SIn the method for preparing the diaryl methyl substituted chiral organic phosphonate compound, the catalyst is selected from sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium phosphate, sodium hydroxide, triethylamine,N,N-dimethylaniline.
The chiral P (O) -H compound and the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound are synthesized into the compound with high stereoselectivityR-/SIn the method for substituting the chiral organic phosphonate compound by the diarylmethyl, the molar ratio of the P (O) -H compound to the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound is 1: [1.0 to 1.2 ]](ii) a The molar ratio of the P (O) -H compound to the catalyst is 1: [0.01 to 0.2 ]]。
The invention provides a method for synthesizing chiral P (O) -H compound and 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-ketone compound with high stereoselectivityR-/SThe method for substituting the chiral organic phosphonate compound by the diaryl methyl has mild and easily controlled reaction process. The method is simple and easy to implement while obtaining higher yield and 100 percent stereoselectivity, avoids the chiral resolution method in the traditional chiral compound synthesis process, and has cheap and easily-used catalystThe preparation method is simple and has good industrial application prospect.
[ detailed description ] embodiments
The invention is further illustrated below with reference to examples of the invention:
first, testing and analyzing
The structural analysis of the reaction products in the following examples of the present invention employed GC/MS (6890N/5973N) gas-mass spectrometer equipped with HP-5MS capillary chromatography column (30 m.times.0.45 mm.times.0.8 μm) manufactured by Agilent and Bruker Avance-III 500 NMR analyzer manufactured by Bruker. The target product selectivity and yield were analyzed using a Bruker Avance-III 500 NMR analyzer manufactured by Bruker.
Second, example
Example 1
140 mg (0.5 mmol) of (Rp) -Phenylphosphonic acid menthyl ester, 176.4 mg (0.6 mmol) of 4-phenylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 0.1 mmol of catalyst (sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium phosphate, sodium hydroxide, triethylamine, potassium chloride, potassium,N,NDimethylaniline) with 1.0 mL of acetonitrile under nitrogen were added to a Schlenk tube at 80 deg.CoC stirring the reaction for 12 hours. By passing31The yield of the 1, 6-addition reaction can reach 89% when cesium carbonate is used as a catalyst, according to the detection and analysis of P NMR nuclear magnetic yield, whereinRp- (-) -menthol group- ((R) The yield of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -phenylphosphonate was 46%,Rp- (-) -menthol group- ((S) 43% of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -phenylphosphonic acid.
Example 2
140 mg (0.5 mmol) of (Rp) -Phenylphosphonic acid menthyl ester, 176.4 mg (0.6 mmol) of 4-phenylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one, cesium carbonate (0.005 mmol, 0.01 mmol, 0.025 mmol, 0.05 mmol, 0.1 mmol), and 1.0 mL of acetonitrile were added under nitrogen to a Schlenk tube at 80 deg.FoC stirring the reaction for 12 hours. By passing31P NMR nuclear magnetic yield detection and analysis, when the dosage of cesium carbonate is 0.05 mAt mol, the yield of the 1, 6-addition reaction can reach 88 percent, whereinRp- (-) -menthol group- ((R) The yield of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -phenylphosphonate was 46%,Rp- (-) -menthol group- ((S) 42% of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -phenylphosphonic acid ester.
Example 3
140 mg (0.5 mmol) of (Rp) -Phenylphosphonic acid menthyl ester, 176.4 mg (0.6 mmol) of 4-phenylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 0.05 mmol of cesium carbonate and 1.0 mL of an organic solvent (dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, methanol, dioxane, toluene, and mixtures thereof,N, NDimethylformamide) under nitrogen atmosphere into a Schlenk tube at 80oC stirring the reaction for 12 hours. By passing31The yield of the 1, 6-addition reaction can reach 88% when the selected organic solvent is acetonitrile according to the detection and analysis of P NMR nuclear magnetic yield, whereinRp- (-) -menthol group- ((R) The yield of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -phenylphosphonate was 46%,Rp- (-) -menthol group- ((S) 42% of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -phenylphosphonic acid ester.
Example 4
140 mg (0.5 mmol) of (Rp) -Phenylphosphonic acid menthyl ester, 4-phenylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one (0.5 mmol, 0.55 mmol, 0.6 mmol), 0.05 mmol cesium carbonate and 1.0 mL acetonitrile were added under nitrogen to a Schlenk tube at 80 deg.CoC stirring the reaction for 12 hours. By passing31P NMR nuclear magnetic yield detection analysis shows that when the selected 4-phenylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one is 0.5 mmol, the 1, 6-addition reaction can reach 88% yield, whereinRp- (-) -menthol group- ((R) The yield of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -phenylphosphonate was 46%,Rp- (-) -menthol group- ((S) 42% of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -phenylphosphonic acid ester.
Example 5
140 mg of (A)0.5 mmol) of (Rp) -Phenylphosphonic acid menthyl ester, 154 mg (0.5 mmol) of 4- (4-methylphenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one, 0.05 mmol of cesium carbonate and 1.0 mL of acetonitrile were added under nitrogen to a Schlenk tube at 80 deg.FoC stirring the reaction for 12 hours. After the reaction is finished, the yield of the 1, 6-addition reaction can reach 69 percent through column chromatography separation and purification, whereinRp- (-) -menthol group- ((R) The yield of (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-methylphenyl) methyl) -phenylphosphonate was 37%,Rp- (-) -menthol group- ((S) 32% of (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-methylphenyl) methyl) -phenylphosphonic acid ester.
Example 6
140 mg (0.5 mmol) of (Rp) -Phenylphosphonic acid menthyl ester 175 mg (0.5 mmol) of 4- (4-tert-butylphenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one, 0.05 mmol of cesium carbonate and 1.0 mL of acetonitrile are introduced under nitrogen into a Schlenk tube at 80%oC stirring the reaction for 12 hours. After the reaction is finished, the 1, 6-addition reaction is separated and purified by column chromatography, and the yield of the 1, 6-addition reaction can reach 76 percent, whereinRp- (-) -menthol group- ((R) The yield of (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-tert-butylphenyl) methyl) -phenylphosphonate was 41%,Rp- (-) -menthol group- ((S) 35% of (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-tert-butylphenyl) methyl) -phenylphosphonate.
Example 7
140 mg (0.5 mmol) of (Rp) -menthyl 2,4, 6-trimethylphenylphosphonate, 147 mg (0.5 mmol) of 4- (phenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 0.05 mmol of cesium carbonate and 1.0 mL of acetonitrile were added under nitrogen to a Schlenk tube at 80 deg.foC stirring the reaction for 12 hours. After the reaction is finished, the yield of the 1, 6-addition reaction can reach 80 percent through column chromatography separation and purification, whereinRp- (-) -menthol group- ((R) The yield of (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-tert-butylphenyl) methyl) -2,4, 6-trimethylphenylphosphonate is 58%,Rp- (-) -menthol group- ((S) - (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-tert-butylphenyl) methyl) -2,4, 6-trimethylphenylphosphonate at 22%.
Example 8
147 mg (0.5 mmol) of (Rp) -Benzylphosphonic acid menthyl ester 147 mg (0.5 mmol) of 4- (phenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one, 0.05 mmol of cesium carbonate and 1.0 mL of acetonitrile were introduced under nitrogen into a Schlenk tube at 80%oC stirring the reaction for 12 hours. After the reaction is finished, the yield of the 1, 6-addition reaction can reach 85 percent through column chromatography separation and purification, whereinSp- (-) -menthol group- ((R) The yield of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -benzylphosphonate was 44%,Sp- (-) -menthol group- ((S) 41% of (3, 5-di-tert-butyl-4-hydroxyphenyl) (phenyl) methyl) -benzylphosphonate.
Example 9
147 mg (0.5 mmol) of (Rp) -Benzylphosphonic acid menthyl ester 186 mg (0.5 mmol) of 4- (4-bromophenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one, 0.05 mmol of cesium carbonate and 1.0 mL of acetonitrile were added under nitrogen to a Schlenk tube at 80%oC stirring the reaction for 12 hours. After the reaction is finished, the 1, 6-addition reaction is separated and purified by column chromatography, and the yield of the 1, 6-addition reaction can reach 76 percent, whereinSp- (-) -menthol group- ((R) The yield of (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-bromophenyl) methyl) -benzylphosphonate was 39%,Sp- (-) -menthol group- ((S) 37% of (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-bromophenyl) methyl) -benzylphosphonate.
Example 10
147 mg (0.5 mmol) of (Rp) -Benzylphosphonic acid menthyl ester, 200 mg (0.5 mmol) of 4- (4-benzyloxyphenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one, 0.05 mmol of cesium carbonate and 1.0 mL of acetonitrile were added under nitrogen to a Schlenk tube at 80 deg.FoC stirring the reaction for 12 hours. After the reaction is finished, the yield of the 1, 6-addition reaction can reach 83 percent through column chromatography separation and purification, whereinSp- (-) -menthol group- ((R) - (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-benzyloxyphenyl) methyl) -The yield of benzylphosphonate was 40%,Sp- (-) -menthol group- ((S) 43% of (3, 5-di-tert-butyl-4-hydroxyphenyl) (4-benzyloxyphenyl) methyl) -benzylphosphonate.
As can be seen from the above examples, the chiral P (O) -OH compound and the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one compound adopted by the invention are utilized to synthesize the compound containing the chiral P (O) -OH with high stereoselectivityR-/SThe method for substituting the chiral organic phosphonate compound by the diaryl methyl has the advantages of mild reaction conditions, cheap and easily obtained catalyst, simple preparation and the like. In addition, the method has the advantages of wide substrate applicability, high yield, high stereoselectivity (100%), no need of chemical chiral resolution and the like, and provides a method for efficiently synthesizing the chiral organic phosphate derivatives containing different substituted functional groups.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (3)
1. A compound with structural formula is prepared by chiral P (O) -H compound and 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-ketone compound through 1, 6-addition reaction by utilizing chiral induction effect（I）The method for substituting chiral organic phosphonate containing R-/S-diarylmethyl in A and B comprises the following steps:
the method is characterized by comprising the following steps:
taking reaction amount of chiral P (O) -H compound, 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadiene-1-one, catalyst and organic solventThe solvent is placed in a reaction vessel to be mixed under the condition of nitrogen, and is reacted for 6 to 12 hours at the temperature of 25 to 100 ℃ under stirring, so that the corresponding functional groups containing different substitutions are preparedR-/S-diarylmethyl substituted chiral organophosphonate derivatives; to produceR-/SThe-diaryl methyl substituted chiral organic phosphonate compound can be separated and purified by a column chromatography separation method;
wherein the content of the first and second substances,
R1is phenyl, 2,4, 6-trimethylphenyl, benzyl;
R2is a menthol group;
ar is phenyl, 4-bromophenyl, 4-benzyloxyphenyl, 4-methylphenyl, 4-tert-butylphenyl;
the catalyst is cesium carbonate, and the organic solvent is acetonitrile;
the molar ratio of the chiral P (O) -H compound to the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one compound is [ 1: 1 ];
the molar ratio of chiral p (o) -H compound to catalyst is [ 1: 0.1].
2. The process according to claim 1, wherein the chiral P (O) -H type compound is selected from (A), (B), (CRp-phenylphosphonic acid menthyl ester, (iii) p-phenylphosphonic acid menthyl esterRp-menthyl 2,4, 6-trimethylphenylphosphonate,(s) ((s))Rp) -benzyl phosphonate menthyl ester.
3. The method according to claim 1, wherein the 4-arylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one is selected from the group consisting of 4-phenylmethylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 4- (4-bromophenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 4- (4-benzyloxyphenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, 4- (4-methylphenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one, and mixtures thereof, 4- (4-tert-butylphenyl) methylene-2, 6-di-tert-butyl-2, 5-cyclohexadien-1-one.
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