JP3531176B2 - Method for producing optically active silyl compounds - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel method for producing an optically active silyl compound. [0002] General formula 1 (Wherein, R ¹ is a lower alkyl group, a C 5-8 cycloalkyl group, an aryl group or a C 5-6 heterocycle, R ² is a hydrogen atom or a lower alkyl group, X is a halogen atom, —OCOO-lower alkyl, —OCO-lower alkyl, —OCO-phenyl, —O-tosyl or —O-mesyl, and R ¹ and R ² may together form a ring. R ^{3 to} R ⁵ are the same or different and each represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxyl group, or an aryl group. And an olefin moiety can be converted into an aldehyde, a carboxylic acid, an epoxy or the like, and are important as an intermediate of an optically active drug or the like. Heretofore, as a method for producing such an optically active silyl compound, there has been known a method for silylating an allyl compound using a metal catalyst modified with a ferrocenylphosphine derivative. (Preprints of the 63rd Annual Meeting of the Chemical Society of Japan, 2F208) However, in such a method using a metal catalyst modified with a ferrocenylphosphine derivative, the formation ratio of the target compound and by-products in the total reaction products Is about 1: 4, the ratio of by-products is very high, and the optical purity of the target compound is also very low at 50% ee.
It was not a practical method. [0004] In view of the above,
The present inventors have studied a method for producing the desired optically active silyl compound represented by the general formula 1 with a low generation ratio of by-products and high optical purity.
The present invention has been reached. [0005] The present invention provides a compound represented by the following general formula: (Wherein, R ¹ and R ² have the same meaning as described above, and X represents a halogen atom, —OCOO-lower alkyl, —OCO—
Represents lower alkyl, -OCO-phenyl, -O-tosyl or -O-mesyl. And allyl compounds represented by), the general formula of ^{3 R 3 R 4 R 5 SiSiR} 6 R 7 R 8 ( wherein, R ³ to R ⁵ are as defined above, R ⁶ to R
⁸ is the same or different and represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxyl group, or an aryl group. ) Is converted to a compound represented by the general formula (Wherein, R ⁹ is a methyl group or an ethyl group, R ¹⁰ and R ¹¹ are the same or different and are each a hydrogen atom, a lower alkyl group,
It represents a hydroxyalkyl group or a bis (hydroxyalkyl) alkyl group. Asymmetric silylation reaction is carried out in the presence of a mixture of an optically active ruthenosenylphosphine derivative represented by the formula (1) and a palladium complex, which produces the optically active silyl compound represented by the formula (1). Is the law. In the method of the present invention, in the allyl compound represented by the general formula (2) as a raw material, the lower alkyl group for the substituent R ¹ includes methyl, ethyl, propyl, butyl, etc., and cycloalkyl having 5 to 8 carbon atoms. cyclopentyl as the alkyl group, cyclohexyl, cyclooctyl, phenyl and the aryl group, tolyl, xylyl, etc., pyranyl as heterocyclic 5 to 6 carbon atoms, pyridyl, piperidyl, etc. are exemplified, of the substituents R ² Examples of the lower alkyl group include methyl, ethyl, propyl, and butyl, and examples of the halogen atom for the substituent X include chloro and bromo, such as -OCO-lower alkyl and -OCO.
Examples of the lower alkyl in O-lower alkyl include methyl, ethyl, propyl, butyl and the like. Specific examples of such allyl compounds include crotyl chloride, 1-phenyl-3-chloropentene, 2-butenyl acetate, 2-butenyl carbonate, and 3-chloro-1-cyclohexene. Is done. In the disilanes represented by the general formula (3), which are silylating agents, chloro, bromo and the like are used as the halogen atoms of the substituents R ^{3 to} R ⁸ , and methyl, ethyl, propyl and the like are used as the lower alkyl groups. Butyl and the like, methoxy, ethoxy, propoxy and butoxy as the lower alkoxyl group, phenyl and the aryl group as the aryl group.
Tolyl, xylyl and the like are exemplified. Specific examples of such disilanes include 1-chloro-1,1-diphenyl-2,2,2-trimethyldisilane, 1,1,1-trichloro-2,2,2-
Trimethyldisilane, 1,1-dichloro-1-phenyl-2,2-dichloro-2-phenyldisilane, 1,1-
Dichloro-1-phenyl-2,2,2-trimethyldisilane is exemplified. The allyl compound represented by the general formula (2) is reacted with the disilane represented by the general formula (3) to give an optically active silyl compound represented by the general formula (1) in good yield.
The selection of a catalyst is extremely important for obtaining a high optical purity, and in the present invention, an optically active ruthenosenylphosphine derivative represented by the above general formula (4) and a palladium complex are used.
A mixture with the body is used. In the optically active ruthenocenylphosphine derivative represented by the general formula 4, methyl, ethyl, propyl, butyl and the like are used as the lower alkyl group for the substituents R ¹⁰ and R ^11, and methyl and methyl are used as the alkyl group. Ethyl, propyl, butyl, hexyl, octyl,
Decyl and the like are exemplified, and specifically, the following compounds are exemplified. (R) -N, N-dimethyl-1-[(S) -1 ′, 2-
Bis (diphenylphosphino) rutenocenyl] ethylamine, (R) -N, N-dimethyl-1-[(S) -1 ′, 2-
Bis (diphenylphosphino) rutenocenyl] propylamine, (R) -N-methyl-N-oxyethyl-1-[(S)
-1 ', 2-bis (diphenylphosphino) rutenocenyl] ethylamine. Such an optically active ruthenocenylphosphine derivative represented by the general formula (4) is, for example, Bul
1, Chem, Soc, Jpn. , Vol. 53, 1138
Page (1980), Acc, Chem, Res. , First
5, 395 (1982), J. Organome.
t, Chem. , No. 382, p. 19 (1990) and the like. The metal catalyst in the present invention is one modified with such an optically active ruthenocenylphosphine derivative, and typically, di-μ-chlorobis (π-allyl) dipalladium [PdCl (η _³ -C ³ H _5)] and a palladium complex and an optically active ruthenate placed sulfonyl phosphine derivative ₂ or the like mixed in a reaction system used. At this time, the amount of the optically active rutenocenylphosphine derivative used is
The amount is usually 1 to 5 times, preferably 2 to 3 times the molar amount of the palladium complex. In the method of the present invention, the use ratio (molar ratio) of the allyl compound represented by the general formula (2) and the disilanes represented by the general formula (3) is usually 1: 1 to 2, preferably 1: 1. 05 to 1.5. The amount of the mixture of the optically active rutenocenyl phosphine derivative and the palladium complex is defined as the amount of the optically active ruthenosenyl phosphine derivative with respect to the allyl compound represented by the general formula (2). 0.01 to 10 mol%, preferably 0.1 to 2
The reaction is usually carried out in a solvent, and examples of the solvent include ethers such as tetrahydrofuran and ethyl ether, aromatic hydrocarbons such as benzene and toluene, and aliphatic hydrocarbons such as hexane and heptane. However, ethers are preferably used. The amount of the solvent to be used is generally 1 to 500 times by weight, preferably 5 to 50 times by weight, relative to the allyl compound represented by the general formula 2 as a raw material. The reaction temperature is -20 to 100C, preferably 0 to 3C.
The reaction time is 0 ° C., and the reaction time is not particularly limited, but is generally 1 to 50 hours. After completion of the reaction, the target compound may be separated by a general method, or in some cases, the silyl group may be converted to a hydroxyl group or the like by using the reaction mixture as it is, and then separated. In this reaction, the configuration of the optically active silyl compound to be produced can be controlled by changing the configuration of the optically active ruthenocenylphosphine derivative which is a catalyst component. . As described above, according to the method of the present invention, the desired optically active silyl compound represented by the above general formula 1 can be produced with a low proportion of by-products and a high optical purity. can do. EXAMPLES The present invention will be described below with reference to examples, but it goes without saying that the present invention is not limited to these examples. EXAMPLE 1 Di-μ-chlorobis (π-allyl) dipalladium [PdCl (η ^3-
C ₃ H _{5)] 2} 2 mg (0.005 mmol) and (R) -N, N-dimethyl-1 - [(S) -1 ', 2-
Bis (diphenylphosphino) rutenocenyl] propylamine (7.5 mg, 0.011 mmol) was added, and dried tetrahydrofuran (2 ml) was added for dissolution. To this solution was added 0.01 ml (1 mmol) of crotyl chloride and 1,1-dichloro-1-phenyl-2,2,2.
272 mg (1.1 mmol) of 2-trimethyldisilane
Was added and stirred at 20 ° C. for 26 hours. Thereafter, the reaction solution was cooled in an ice bath, diluted with 10 ml of dry ether, added with 0.3 ml of ethanol and 0.5 ml of triethylamine, and stirred at room temperature for 1 hour. The produced ammonium salt was removed by filtration using Celite, and the filtrate was concentrated under reduced pressure. Kugel distillation of concentrated residue (bath temperature 15
0 ° C./0.2 mmHg) to give 201 mg of the silylated product
(0.803 mmol, 80% yield). The silylated product is 2- (phenyldiethoxysilyl) -3-
It was a mixture of butene and 1-fu (phenyldiethoxysilyl) -2-butene in a ratio of 42:52. The obtained mixture was alcoholized by a conventional method, and purified by column chromatography to obtain (S) -3-buten-2-ol. The optical purity of this product was analyzed by a conventional method.
2%.

──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) C07F 7/18 C07F 7/08 B01J 31/28 C07B 53/00 C07B 61/00 300 CA (STN) CAOLD ( STN) REGISTRY (STN)

Claims (1)

(57) [Claims] [Claim 1] General formula 2 (Wherein, R ¹ is a lower alkyl group, a C 5-8 cycloalkyl group, an aryl group or a C 5-6 heterocycle, R ² is a hydrogen atom or a lower alkyl group, X is a halogen atom, —OCOO-lower alkyl, —OCO-lower alkyl, —OCO-phenyl, —O-tosyl or —O-mesyl, and R ¹ and R ² may together form a ring. ) And a general formula 3 R ³ R ⁴ R ⁵ SiSiR ⁶ R ⁷ R ⁸ (wherein R ^{3 to} R ⁸ are the same or different and each represent a hydrogen atom,
Halogen atom, lower alkyl group, lower alkoxyl group,
Indicates an aryl group. ) Is converted to a compound represented by the general formula (In the formula, R ⁹ represents a methyl group or an ethyl group, and R ¹⁰ and R ¹¹ represent a hydrogen atom, a lower alkyl group, a hydroxyalkyl group or a bis (hydroxyalkyl) alkyl group.) Wherein the asymmetric silylation reaction is carried out in the presence of a mixture of a nylphosphine derivative and a palladium complex. (Wherein, R ^{1 to} R ⁵ have the same meanings as described above).