CN109503656A - A kind of chiral induction efficiently prepares the new method of the substituted chiral Organophosphonate of diarylmethyl containing R-/S- - Google Patents
A kind of chiral induction efficiently prepares the new method of the substituted chiral Organophosphonate of diarylmethyl containing R-/S- Download PDFInfo
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- CN109503656A CN109503656A CN201811431075.XA CN201811431075A CN109503656A CN 109503656 A CN109503656 A CN 109503656A CN 201811431075 A CN201811431075 A CN 201811431075A CN 109503656 A CN109503656 A CN 109503656A
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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
- C07F9/3258—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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
A kind of method the present invention provides efficient, high selectivity chirality containing the different R-/S- diarylmethyl substituted chiral Organophosphonate analog derivatives for replacing functional groups, it uses cesium carbonate as catalyst, with chiral P (O)-H compound and 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone compounds are as reaction substrate.Reaction system joined organic solvent.The advantages of this method: catalyst is cheap and easy to get；Substrate applicability is high；Reaction condition is mild, securely and reliably；The three-dimensional enantioselectivity of gained target product is greater than 99%, and yield is up to 80% or more.This method solve the reaction enantioselectivities of conventional synthesis chirality R-/S- diarylmethyl substituted chiral Organophosphonate analog derivative it is poor, reaction step is cumbersome the deficiencies of, evaded traditional chiral separation method, have good prospects for commercial application.The present invention additionally provides corresponding containing the different chiral R-/S- diarylmethyl substituted chiral Organophosphonate analog derivatives for replacing functional group simultaneously.
Description
Technical field
The present invention relates to the applied catalysis of chiral organic phosphonates compound to synthesize field, relate in particular to it is a kind of with
Chiral P (O)-H compound and the high three-dimensional choosing of 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone compounds
The preparation side of the 1,6- addition reaction preparation substituted chiral of diarylmethyl containing R-/S- Organophosphonate analog derivative occurs for selecting property
Method.
Background technique
R-/S- diarylmethyl substituted chiral Organophosphonate is a kind of important organic intermediate.They are in chiral medicine
Object, anticancer agent, preparation etc. the extensive application of efficient flame-retarding agent and chiral catalyst ligand.Match in various differences
In the organic phosphorus compound of position, one, two and the research of hexa-coordinate compound be newest inchoate work, they are as organic conjunction
It is not yet mature at the technique of building block.Organophosphorus reagent is mainly limited to three, four, Phosphorane compound, especially three or four at present
Complex has a wide range of applications when carrying out organic synthesis or phosphate functional modification.
Pentacoordinate phosphinylidyne reagent is finally all converted to the phosphorus compound of four-coordination during phosphorus acylation reaction, especially contains
The four-coordination phosphorus compound of the phosphoryl (P=O) of Jiang Gao's energy.Three four-coordination phosphorus reagents, mainly four-coordination phosphorus reagent, are reacting
In the process, often again using Phosphorane compound as intermediate or transition state, just because of this different ligancy compounds
Between mutually convert, organophosphorus reagent just is widely applied in organic synthesis, becomes organophosphorus chemistry, especially has
The important component of machine synthesis chemistry.
The reported synthesis of diaryl methyl of document replaces the method for Organophosphonate to specifically include that (1) at presentFriedel-CraftsReaction: using containing P (O)-H or P (O)-X class compound and 1,1- diaryl substituted alcohols (hydrocarbon) class compound
Coupling reaction occurs under the catalysis of ferric trichloride；(2) nucleophilic coupling reaction: using P (O)-H class compound in transition metal
Its cross-coupling reaction for replacing halogenated hydrocarbons with 1,1- diaryl is catalyzed in the presence of the reagents such as (iron, copper, nickel, palladium etc.) and alkali；
(3) arylation reaction: organic phosphonates compound and halogenated aromatic the urging in transition metal replaced containing α-benzyl is utilized
Change lower generation cross-coupling reaction；(4) 1,6- addition reaction: two uncle of P (O)-H compound and 4- aryl methylene -2,6- is utilized
Corresponding 1,6- occurs under the catalysis of Cabbeen particular ligand or transition metal for butyl -2,5- cyclohexadiene -1- ketone compounds
Addition reaction: it is anti-that cross-coupling is carried out with nucleopilic reagent alcohol under angiotensins catalytic condition using P (O)-OR class compound
It answers；(5) Arbuzov reacts: preparing diarylmethyl with alkyl halide effect as nucleopilic reagent using trialkyl phosphite and takes
For organophosphorus ester.But at present about containingR-/SThe synthetic method of diarylmethyl substituted chiral organic phosphonate compounds
It is not yet reported that and the above method be generally used the reagent (P (OR) to air-sensitive3Compound, phosphoryl chloride phosphorus oxychloride etc.), special match
Body (ferrocene ligands, carbenes etc.) and transition-metal catalyst (iron, copper, nickel, palladium etc.), but also there is experimental procedures
Cumbersome, expensive catalyst and being difficult to recycles, severe reaction conditions, substrate applicability intersect, yield is lower and to environment
Pollution it is larger the defects of.
So far, containR-/SDiarylmethyl substituted chiral organic phosphonates compound efficiently synthesize there is
Material quality, the safety (compounds such as trialkyl phosphite and phosphoryl chloride phosphorus oxychloride have stronger corrosivity) of production, chirality
Split that difficulty is big and the problem of several aspects such as the stability of product and purity, synthetic technology difficulty is larger, at present only beauty,
Several companies of Deng state are producing, and the high-end chiral Organophosphonate product present case in China be mainly fixed against into
Mouthful.
For the deficiency of existing chiral Organophosphonate synthesis technology, industry is just being put forth effort on efficient using cheap catalyst
Catalysis, which is developed, synthesizes corresponding contain as phosphorus esterification reagent by stabilization, chiral P (O)-H compound cheap and easy to getR-/S- two virtues
The new method of ylmethyl substituted chiral organic phosphonates compound.
Summary of the invention
The object of the present invention is to provide a kind of by chiral P (O)-H compound and 4- aryl methylene -2,6- cheap and easy to get
Di-t-butyl -2,5- cyclohexadiene -1- ketone compounds carry out 1,6- addition reaction as raw material, utilize phosphorus chiral centre Gao Li
Body selectively induces the new method that chiral quaternary carbon is formed, to overcome drawbacks described above in the prior art.
One object of the present invention provide it is a kind of by chiral P (O)-H compound cheap and easy to get and aryl methylene -2 4-,
Synthesize corresponding contain to 6- di-t-butyl -2,5- cyclohexadiene -1- ketone compounds highly-solid selectivelyR-/SDiarylmethyl
The new method of substituted chiral organic phosphonates compound, specific reaction equation are as follows:
(I)
It is characterized in that, including following step:
It takes chiral P (the O)-H compound of reacting dose, 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, urge
Agent and organic solvent are placed in reaction vessel under a nitrogen atmosphere to be mixed, and reacts 6 ~ 12 at 25 ~ 100 DEG C under stiring
Hour, it obtains accordingly containing different substitution functional groupsR-/SDiarylmethyl substituted chiral Organophosphonate analog derivative.
It is obtainedR-/SDiarylmethyl substituted chiral organic phosphonate compounds (A and B) (are washed using column chromatography chromatogram partition method
De- agent: petroleum ether: ethyl acetate=2:1 ~ 5:1) realize separating-purifying；
Wherein,
R1It is phenyl, 2,4,6- trimethylphenyl, benzyl；
R2It is peppermint alcohol radical；
Ar is phenyl, 4- bromophenyl, 4- benzyloxy-phenyl, 4- aminomethyl phenyl, 4- tert-butyl-phenyl.
It is above-mentioned by chiral P (O)-H compound and 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone
Compound high stereoselectivity synthesis containsR-/SIn the method for diarylmethyl substituted chiral organic phosphonates compound, hand
Property P (O)-H compound be selected from (RP)-phenyl-phosphonic acid menthol ester, (RP) -2,4,6- trimethylphenyl phosphonic acids menthol ester,
(RP)-benzylphosphonic acid menthol ester.
It is above-mentioned by chiral P (O)-H compound and 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone
Compound high stereoselectivity synthesis containsR-/SIn the method for diarylmethyl substituted chiral organic phosphonates compound, institute
Stating 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone compounds is selected from selected from 4- phenylmethylene -
2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 4- (4- bromophenyl) methylene -2,6- di-t-butyl -2,5- cyclohexadiene -
1- ketone, 4- (4- benzyloxy-phenyl) methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 4- (4- aminomethyl phenyl) methylene
Base -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 4- (4- tert-butyl-phenyl) methylene -2,6- di-t-butyl -2,5- ring
Hexadiene -1- ketone.
It is above-mentioned by chiral P (O)-H compound and 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone
Compound high stereoselectivity synthesis containsR-/SIn the method for diarylmethyl substituted chiral organic phosphonates compound, institute
State organic solvent be methylene chloride, dichloroethanes, tetrahydrofuran, acetonitrile, methanol, dioxane, toluene,N, NDimethyl methyl
Amide.
It is above-mentioned by chiral P (O)-H compound and 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone
Compound high stereoselectivity synthesis containsR-/SIn the method for diarylmethyl substituted chiral organic phosphonates compound, institute
State catalyst be selected from sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium phosphate, sodium hydroxide, triethylamine,N,NDimethyl
Aniline.
It is above-mentioned by chiral P (O)-H compound and 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone
Compound high stereoselectivity synthesis containsR-/SIn the method for diarylmethyl substituted chiral organic phosphonates compound, institute
It states P (O)-H compound and the molar ratio of 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone compounds is
1:[1.0 ~ 1.2]；The molar ratio of P (the O)-H compound and catalyst is 1:[0.01 ~ 0.2].
It is provided by the present invention by chiral P (O)-H compound and 4- aryl methylene -2,6- di-t-butyl -2,5- hexamethylene two
It synthesizes to alkene -1- ketone compounds highly-solid selectively and containsR-/SDiarylmethyl substituted chiral organic phosphonates compound
Method, reaction process is mildly easy to control.While obtaining higher yields and 100% stereoselectivity, this method is simply easy
Row, the method for avoiding the chiral resolution in traditional chipal compounds synthesis process, and also used catalyst is cheap and easy to get, preparation
Simply, there is good prospects for commercial application.
[specific embodiment]
Below with reference to the embodiment of the present invention, the present invention will be further described:
One, test and analysis
The structural analysis of reaction product uses the configuration HP-5MS capillary of Agilent company production in the following embodiments of the present invention
The gas phase of chromatographic column (30m × 0.45mm × 0.8 μm)-mass spectrograph combined instrument GC/MS (6890N/5973N) and Bruker is public
Take charge of 500 magnetic nuclear resonance analyzer of Bruker Avance-III of production.Target product selectivity and yield then use by
500 magnetic nuclear resonance analyzer of Bruker Avance-III of Bruker company production is analyzed.
Two, embodiment
Embodiment 1
By 140 mg (0.5 mmol) (RP)-phenyl-phosphonic acid menthol ester, the 4- phenyl of 176.4 mg (0.6 mmol) are sub-
Catalyst (sodium carbonate, potassium carbonate, cesium carbonate, the carbon of methyl -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 0.1 mmol
Sour hydrogen sodium, potassium phosphate, sodium hydroxide, triethylamine,N,NDimethylaniline) it is added in a nitrogen environment with 1.0 mL acetonitriles
In Schlenk pipe, in 80oC is stirred to react 12 hours.Pass through31P NMR nuclear-magnetism yield tests and analyzes, in cesium carbonate as catalysis
When agent, the yield of 1, the 6- addition reaction can reach 89% yield, whereinRP- (-)-peppermint alcohol radical-((RBis- uncle of)-(3,5-
Butyl -4- hydroxy phenyl) (phenyl) methyl)-phenyl phosphonic acid esters yield be 46%,RP- (-)-peppermint alcohol radical-((S)-(3,
5- di-tert-butyl-hydroxy phenyl) (phenyl) methyl)-phenyl phosphonic acid esters be 43%.
Embodiment 2
By 140 mg (0.5 mmol) (RP)-phenyl-phosphonic acid menthol ester, the 4- phenyl of 176.4 mg (0.6 mmol) are sub-
Methyl -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, cesium carbonate (0.005 mmol, 0.01 mmol, 0.025 mmol,
0.05 mmol, 0.1 mmol) it is added in Schlenk pipe in a nitrogen environment with 1.0 mL acetonitriles, in 80oC is stirred to react
12 hours.Pass through31P NMR nuclear-magnetism yield tests and analyzes, when the dosage of cesium carbonate is 0.05 mmol, 1, the 6- addition reaction
Yield can reach 88% yield, whereinRP- (-)-peppermint alcohol radical-((R)-(3,5- di-tert-butyl-hydroxy phenyl) (benzene
Base) methyl)-phenyl phosphonic acid esters yield be 46%,RP- (-)-peppermint alcohol radical-((S)-(3,5- di-t-butyl -4- hydroxy benzenes
Base) (phenyl) methyl)-phenyl phosphonic acid esters be 42%.
Embodiment 3
By 140 mg (0.5 mmol) (RP)-phenyl-phosphonic acid menthol ester, the 4- phenyl of 176.4 mg (0.6 mmol) are sub-
Methyl -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 0.05 mmol cesium carbonate and 1.0 mL organic solvent (dichloromethanes
Alkane, dichloroethanes, tetrahydrofuran, acetonitrile, methanol, dioxane, toluene,N, NDimethylformamide) add in a nitrogen environment
Enter in Schlenk pipe, in 80oC is stirred to react 12 hours.Pass through31P NMR nuclear-magnetism yield tests and analyzes, when selected organic molten
When agent is acetonitrile, the yield of 1, the 6- addition reaction can reach 88% yield, whereinRP- (-)-peppermint alcohol radical-((R)-(3,
5- di-tert-butyl-hydroxy phenyl) (phenyl) methyl)-phenyl phosphonic acid esters yield be 46%,RP- (-)-peppermint alcohol radical-
((S)-(3,5- di-tert-butyl-hydroxy phenyl) (phenyl) methyl)-phenyl phosphonic acid esters be 42%.
Embodiment 4
By 140 mg (0.5 mmol) (RP)-phenyl-phosphonic acid menthol ester, di-t-butyl -2 4- phenylmethylene -2,6-,
5- cyclohexadiene -1- ketone (0.5 mmol, 0.55 mmol, 0.6 mmol), 0.05 mmol cesium carbonate and 1.0 mL acetonitriles
It is added in Schlenk pipe in a nitrogen environment, in 80oC is stirred to react 12 hours.Pass through31P NMR nuclear-magnetism yield tests and analyzes,
When the dosage of selected 4- phenylmethylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone is 0.5 mmol, this 1,6-
The yield of addition reaction can reach 88% yield, whereinRP- (-)-peppermint alcohol radical-((R)-(3,5- di-t-butyl -4- hydroxyl
Phenyl) (phenyl) methyl)-phenyl phosphonic acid esters yield be 46%,RP- (-)-peppermint alcohol radical-((S)-(3,5- di-t-butyl-
4- hydroxy phenyl) (phenyl) methyl)-phenyl phosphonic acid esters be 42%.
Embodiment 5
By 140 mg (0.5 mmol) (RP) 4- (the 4- methyl of-phenyl-phosphonic acid menthol ester, 154 mg (0.5 mmol)
Phenyl) methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 0.05 mmol cesium carbonate and 1.0 mL acetonitriles are in nitrogen
It is added in Schlenk pipe under environment, in 80oC is stirred to react 12 hours.To after reaction, be mentioned by column chromatography chromatogram separation
Pure, the yield of 1, the 6- addition reaction can reach 69% yield, whereinRP- (-)-peppermint alcohol radical-((RThe tertiary fourth of)-(3,5- bis-
Base -4- hydroxy phenyl) (4- aminomethyl phenyl) methyl)-phenyl phosphonic acid esters yield be 37%,RP- (-)-peppermint alcohol radical-((S)-
(3,5- di-tert-butyl-hydroxy phenyl) (4- aminomethyl phenyl) methyl)-phenyl phosphonic acid esters be 32%.
Embodiment 6
By 140 mg (0.5 mmol) (RP) 4- (the tertiary fourth of 4- of-phenyl-phosphonic acid menthol ester, 175 mg (0.5 mmol)
Base phenyl) methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 0.05 mmol cesium carbonate and 1.0 mL acetonitriles are in nitrogen
It is added in Schlenk pipe under compression ring border, in 80oC is stirred to react 12 hours.To after reaction, be separated by column chromatography chromatogram
Purification, the yield of 1, the 6- addition reaction can reach 76% yield, whereinRP- (-)-peppermint alcohol radical-((RBis- uncle of)-(3,5-
Butyl -4- hydroxy phenyl) (4- tert-butyl-phenyl) methyl)-phenyl phosphonic acid esters yield be 41%,RP- (-)-peppermint alcohol radical-
((S)-(3,5- di-tert-butyl-hydroxy phenyl) (4- tert-butyl-phenyl) methyl)-phenyl phosphonic acid esters be 35%.
Embodiment 7
By 140 mg (0.5 mmol) (RP) -2,4,6- trimethylphenyl phosphonic acids menthol ester, 147 mg (0.5 mmol)
4- (phenyl) methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 0.05 mmol cesium carbonate and 1.0 mL acetonitriles exist
It is added in Schlenk pipe under nitrogen environment, in 80oC is stirred to react 12 hours.To after reaction, divide by column chromatography chromatogram
From purification, the yield of 1, the 6- addition reaction can reach 80% yield, whereinRP- (-)-peppermint alcohol radical-((R)-(3,5- bis-
Tert-butyl-hydroxy phenyl) (4- tert-butyl-phenyl) methyl) -2,4,6- trimethylphenyl phosphonate esters yield be 58%,Rp-
(-)-peppermint alcohol radical-((S)-(3,5- di-tert-butyl-hydroxy phenyl) (4- tert-butyl-phenyl) methyl) -2,4,6- trimethyl
Phenyl phosphonic acid esters are 22%.
Embodiment 8
By 147 mg (0.5 mmol) (RP)-benzylphosphonic acid menthol ester, the 4- (phenyl) of 147 mg (0.5 mmol) are sub-
Methyl -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 0.05 mmol cesium carbonate add in a nitrogen environment with 1.0 mL acetonitriles
Enter in Schlenk pipe, in 80oC is stirred to react 12 hours.To after reaction, by column chromatography chromatogram separating-purifying, this 1,
The yield of 6- addition reaction can reach 85% yield, whereinSP- (-)-peppermint alcohol radical-((R)-(3,5- di-t-butyl -4- hydroxyl
Base phenyl) (phenyl) methyl)-benzylphosphonic acid ester yield be 44%,SP- (-)-peppermint alcohol radical-((SThe tertiary fourth of)-(3,5- bis-
Base -4- hydroxy phenyl) (phenyl) methyl)-benzylphosphonic acid ester be 41%.
Embodiment 9
By 147 mg (0.5 mmol) (RP) 4- (the 4- bromobenzene of-benzylphosphonic acid menthol ester, 186 mg (0.5 mmol)
Base) methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 0.05 mmol cesium carbonate and 1.0 mL acetonitriles are in nitrogen ring
It is added in Schlenk pipe under border, in 80oC is stirred to react 12 hours.To after reaction, be mentioned by column chromatography chromatogram separation
Pure, the yield of 1, the 6- addition reaction can reach 76% yield, whereinSP- (-)-peppermint alcohol radical-((RThe tertiary fourth of)-(3,5- bis-
Base -4- hydroxy phenyl) (4- bromophenyl) methyl)-benzylphosphonic acid ester yield be 39%,SP- (-)-peppermint alcohol radical-((S)-
(3,5- di-tert-butyl-hydroxy phenyl) (4- bromophenyl) methyl)-benzylphosphonic acid ester be 37%.
Embodiment 10
By 147 mg (0.5 mmol) (RP) 4- (the 4- benzyloxy of-benzylphosphonic acid menthol ester, 200 mg (0.5 mmol)
Base phenyl) methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 0.05 mmol cesium carbonate and 1.0 mL acetonitriles are in nitrogen
It is added in Schlenk pipe under compression ring border, in 80oC is stirred to react 12 hours.To after reaction, be separated by column chromatography chromatogram
Purification, the yield of 1, the 6- addition reaction can reach 83% yield, whereinSP- (-)-peppermint alcohol radical-((RBis- uncle of)-(3,5-
Butyl -4- hydroxy phenyl) (4- benzyloxy-phenyl) methyl)-benzylphosphonic acid ester yield be 40%,SP- (-)-peppermint alcohol radical-
((S)-(3,5- di-tert-butyl-hydroxy phenyl) (4- benzyloxy-phenyl) methyl)-benzylphosphonic acid ester be 43%.
As can be seen from the above-described embodiment, of the present invention to utilize chirality P (O)-OH compound and 4- aryl methylene
It synthesizes to base -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone compounds highly-solid selectively and containsR-/SDiarylmethyl
The method of substituted chiral organic phosphonates compound has reaction condition is mild, catalyst is cheap and easy to get and preparation is simple etc.
Advantage.In addition, this method also has wide substrate applicability, high yield, highly-solid selectively (100%) and does not need to utilize change
The advantages that learning chiral resolution provides a kind of efficiently synthesize containing the different chiral organophosphorus ester analog derivatives for replacing functional group
Method.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
Limitations on the scope of the patent of the present invention therefore cannot be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to guarantor of the invention
Protect range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (7)
1. one kind is by chiral P (O)-H compound and 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone
It closes object and 1,6- addition reaction preparation efficiently occurs with structural formula using chiral induction effect(I)Diaryl containing R-/S- in A and B
The preparation method of methyl substituted chiral Organophosphonate is as follows:
(I)
It is characterized in that, including following step:
It takes chiral P (the O)-H compound of reacting dose, 4- aryl methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, urge
Agent and organic solvent are placed in reaction vessel under a nitrogen atmosphere to be mixed, and reacts 6 ~ 12 at 25 ~ 100 DEG C under stiring
Hour, it obtains accordingly containing different substitution functional groupsR-/SDiarylmethyl substituted chiral Organophosphonate analog derivative.
It is obtainedR-/SDiarylmethyl substituted chiral organic phosphonate compounds (A and B) (are washed using column chromatography chromatogram partition method
De- agent: petroleum ether: ethyl acetate=2:1 ~ 5:1) realize separating-purifying.
Wherein,
R1It is phenyl, 2,4,6- trimethylphenyl, benzyl；
R2It is peppermint alcohol radical；
Ar is phenyl, 4- bromophenyl, 4- benzyloxy-phenyl, 4- aminomethyl phenyl, 4- tert-butyl-phenyl.
2. preparation method according to claim 1, which is characterized in that chirality P (the O)-H class compound is to be selected from
(RP)-phenyl-phosphonic acid menthol ester, (RP) -2,4,6- trimethylphenyl phosphonic acids menthol ester, (RP)-benzylphosphonic acid menthol
Ester.
3. preparation method according to claim 1, which is characterized in that the 4- aryl methylene -2,6- di-t-butyl -2,
5- cyclohexadiene -1- ketone is selected from 4- phenylmethylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 4- (4- bromophenyl)
Methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, di-t-butyl -2 4- (4- benzyloxy-phenyl) methylene -2,6-,
5- cyclohexadiene -1- ketone, 4- (4- aminomethyl phenyl) methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone, 4- (the tertiary fourth of 4-
Base phenyl) methylene -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone.
4. preparation method according to claim 1, which is characterized in that the organic solvent be methylene chloride, dichloroethanes,
Tetrahydrofuran, acetonitrile, methanol, dioxane, toluene,N, NDimethylformamide.
5. preparation method according to claim 1, which is characterized in that the catalyst is selected from sodium carbonate, potassium carbonate, carbon
Sour caesium, sodium bicarbonate, potassium phosphate, sodium hydroxide, triethylamine,N,NDimethylaniline.
6. preparation method according to claim 1, which is characterized in that chirality P (the O)-H compound and 4- aryl methylene
The molar ratio of base -2,6- di-t-butyl -2,5- cyclohexadiene -1- ketone compounds is 1:[1.0 ~ 1.2].
7. preparation method according to claim 1, which is characterized in that chirality P (the O)-H compound and catalyst rub
You are than being 1:[0.01 ~ 0.2].
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| CN112010898A (en) * | 2020-08-29 | 2020-12-01 | 湖南理工学院 | Novel method for preparing diaryl methyl substituted phosphonate |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112010898A (en) * | 2020-08-29 | 2020-12-01 | 湖南理工学院 | Novel method for preparing diaryl methyl substituted phosphonate |
| CN112010898B (en) * | 2020-08-29 | 2022-07-12 | 湖南理工学院 | Novel method for preparing diaryl methyl substituted phosphonate |
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