JPH05255351A - Production of optically active silyl compound - Google Patents

Abstract

PURPOSE:To give the subject compounds of high optical purity in high isolation yield with high reproducibility by asymmetric hydrosilylation of an olefin with a silane in the copresence of a transition metal catalyst and an optically active phosphine. CONSTITUTION:The reaction of a compound of formula I (n is 1, 2; R<1>, R<2> are H, alkyl, aralkyl, aryl, alkoxycarbonyl, cyano, nitro; dotted line represents a single or double bond) with a silane of formula III (X, Y, Z are H, alkyl, alkoxy, halogen) is carried out in the copresence of a transition metal catalyst such as allyl-palladium chloride dimer and an optically active phosphine of formula II at -20 to 100 deg.C to give a compound of formula IV. The objective compound of formula IV can be converted into optically active alcohol derivatives, halides by exchange of silyl groups with functional groups. For example, optically active norborneol is useful as a synthetic intermediate of an antagonist of thromboxane A2.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to optically active bicyclo [2.2. n] relates to a method for producing a silyl compound.

[0002]

2. Description of the Related Art Optically active silyl compounds can be easily converted into optically active alcohol derivatives and halogen compounds by converting functional groups of silyl groups into more complex optically active compounds. Can be induced. For example, the optically active norborneol obtained by the method of the present invention is a useful substance as a thromboxane A2 competitive inhibitor intermediate, and the optically active silyl compound is various optically active substances such as pharmaceuticals, agricultural chemicals and ferroelectric liquid crystal materials. It is a compound useful in the production of compounds.

Optically active silyl compounds are obtained by asymmetric hydrosilylation of olefins.

The asymmetric hydrosilylation reaction uses a conjugated diene as a raw material and an optically active ferrocenylphosphine (N, N-dimethyl-1- [2- (diphenylphosphino) ferrocenyl] ethylamine) -palladium complex with trichlorosilane. There are several examples of reactions using asymmetric catalysts (T. Hayashi et al., Tetrahedron asymmetry (T.
etrahedron Asymmetry), 1 , 151 (1990) et al.) and a reaction of trichlorosilane with norbornene and styrene using the same asymmetric catalyst (Tehrahedron Lett.)
21 , 1871 (1980)), but the former is bicyclo [2.2. There is no n] type compound, and the latter has a low optical yield and is problematic in practical use.

From the viewpoint of a method for producing an optically active alcohol, asymmetric hydrolysis of a racemic aliphatic ester by a fermentation method, induction of a racemic alcohol into a diastereomeric mixture, and recrystallization to obtain a desired optically active substance. Although there are conceivable methods, all of them are optical resolution methods and are not efficient because unwanted optical isomers are wasted. In addition, asymmetric reduction of ketones with yeast and asymmetric catalytic hydrogenation reaction with an optically active transition metal complex catalyst are also known as optically active alcohol production methods, but bicyclo [2.2.
It cannot be applied to the [n] -based compound because the starting material ketone already has chirality.

On the other hand, a method for producing an optically active norborneol by an asymmetric hydroboration reaction of an optically active diisopinocamphenylborane to norbornene is known (HC Brown et al., Journal of Organic Chemistry ( J. Org. Che
m.), 51 , 4526 (1986)), where 2 mol or more of the asymmetric source, which is difficult to obtain in large quantities, is used per 1 mol of the raw material, and there is a problem in use on an industrial scale.

[0007]

Means for Solving the Problems As a result of intensive studies in view of such circumstances, the present inventors have found that bicyclo [2.2.
n] -based olefin compound as a raw material, asymmetric hydrosilylation reaction of silanes in the presence of a trace amount of optically active phosphine compound as well as a trace amount of a transition metal catalyst, and good reproducibility,
The inventors have found a method for obtaining a useful optically active silyl compound with high isolation yield and optical purity, and completed the present invention.

The present invention is directed to bicyclo [2.2. [n] -based olefin compound as a raw material, a silane represented by the general formula (III) is reacted in the presence of a transition metal catalyst and an optically active phosphine compound represented by the structural formula (II). Bicyclo [2.2. n] -based optically active silyl compound.

The present invention has the general formula (I):

[0010]

[Chemical 7]

Where n is 1 or 2, R ¹ and R ²
Each independently represents a hydrogen atom, an alkyl group, an aralkyl group, an aryl group, an alkoxycarbonyl group, a cyano group or a nitro group, and a line

[0012]

[Chemical 8]

Means a single bond or a double bond) with a transition metal catalyst and a structural formula (II):

[0014]

[Chemical 9]

In the presence of an optically active phosphine compound represented by the general formula (III):

[0016]

[Chemical 10]

(Wherein X, Y and Z each independently represent a hydrogen atom, an alkyl group, an alkoxyl group or a halogen atom) are reacted with silanes represented by the general formula (IV) :

[0018]

[Chemical 11]

(Where n, R ¹ , R ² and the line

[0020]

[Chemical 12]

Is the same as the above).
2, n] -based method for producing an optically active silyl compound.

The starting olefin compound has the general formula (I):

[0023]

[Chemical 13]

Where n is 1 or 2, R ¹ and R ²
Are each independently a hydrogen atom, an alkyl group, an aralkyl group, an aryl group, an alkoxycarbonyl group, a cyano group or a nitro group, and

[0025]

[Chemical 14]

Represents a single bond or a double bond). Here, the alkyl group is preferably one having 1 to 5 carbon atoms, and the aralkyl group is, for example, benzyl, α-methylbenzyl or β-.
Examples of phenethyl and aryl groups include phenyl and naphthyl, and examples of alkoxycarbonyl groups include methoxycarbonyl and ethoxycarbonyl. Specific examples of the olefin of the general formula (I) include norbornene, bicyclo [2.2.2] octene, norbornadiene, and 5,6-bis (methoxycarbonyl) norbornene, which can be easily synthesized by the Diels-Alder reaction, and 5, 6-dicyanonorbornene or the like is used.

As the transition metal catalyst that can be used in the present invention, a compound having a carbon-carbon double bond, such as a palladium compound or a platinum compound, which coordinates with a phosphine compound and causes an oxidative addition to silanes can be used. . For example, allyl palladium chloride dimer, palladium acetate, palladium chloride, palladium acetylacetonate complex,
Allyl (cyclopentadienyl) palladium, dichlorobis (acetonitrile) palladium, dichlorobis (benzonitrile) palladium, tris (μ-dibenzylideneacetone) dipalladium, potassium trichloro (ethylene) platinate and potassium tetrachloroplatinate . In particular, when a palladium compound is used as a catalyst, a high optical purity is obtained, and when a platinum compound is used as a catalyst, a product is obtained with a high isolation yield.

The amount of the transition metal catalyst used is 0.001 to 1.0 mol%, preferably 0.01 to 0.1 mol%, based on the olefin as a substrate.

The silanes usable in the present invention are represented by the general formula (III):

[0030]

[Chemical 15]

(In the formula, X, Y and Z each independently represent an alkyl group, an alkoxyl group or a halogen atom). Here, as the alkyl group, those having 1 to 3 carbon atoms are preferable, and as the alkoxyl group,
A halogen atom having 1 to 3 carbon atoms is preferable, and a chlorine atom is preferable as the halogen atom. Specific examples of the compound represented by the general formula (III) include trichlorosilane, methyldichlorosilane, trimethoxysilane, triethoxysilane and the like. In particular, the use of trichlorosilane gives excellent results in terms of isolation yield and optical purity. Silanes can be used in excess with respect to the substrate olefin, but the reaction tends to proceed in a high yield even if only 1 equivalent is used.

The optically active phosphine compound (2-diphenylphosphino-2'-methoxy-1,1'-binaphthyl: structural formula (II)) has an (R)-(+)-form and a (S) -form.
Although any configuration of the (-)-form can be used in the reaction, the product and the (S)-(-)-form when the reaction is carried out using the (R)-(+)-form With the product obtained using Therefore, which of the optical isomers of the phosphine compound is to be used may be selected according to the desired configuration of the silyl compound.

The phosphine compound is used in an amount of 1 to 3 equivalents, preferably 2 equivalents, based on the transition metal catalyst.

A reaction solvent may not be used, but if necessary, a solvent inert to the starting materials and silanes (for example, a hydrocarbon solvent such as benzene, toluene, xylene or n-hexane, diethyl ether, An ether solvent such as 1,4-dioxane or tetrahydrofuran (hereinafter referred to as THF) or a halogen solvent such as methylene chloride, chloroform, 1,1 or 1-trichloroethane, etc. can be used.

For example, the production method of the present invention can be carried out as follows, but is not limited to this. A silane compound is added to a mixture of a raw material olefin compound, a transition metal catalyst, and a phosphine compound, and the mixture is stirred for several hours. Alternatively, the transition metal catalyst and the phosphine compound may be mixed in a suitable solvent to prepare a complex in advance, and then the olefin compound and the silane compound may be added and reacted. In most cases the silylated products have relatively low boiling points so that pure products can be isolated by vacuum distillation of the reaction mixture. The reaction proceeds at any reaction temperature, but is preferably -20 ° C to 100 ° C, more preferably -20 ° C.
When the reaction is carried out in the range of 5 to 5 ° C, a product having higher optical purity is obtained.

On the other hand, the thus obtained optically active silyl compound can be easily converted into an alcohol derivative while maintaining the configuration. For example, in the case of a trichlorosilyl compound, it is reacted with ethanol in diethyl ether in the presence of triethylamine to give a triethoxysilyl compound, and when hydrogen peroxide is allowed to act in the presence of potassium bicarbonate in a mixed solvent of tetrahydrofuran and methanol, the silyl group becomes Can be converted to hydroxyl group.

[0037]

[Chemical 16]

[0038]

EXAMPLES Next, the production method of the present invention will be specifically described by way of examples, but these examples do not limit the present invention.

Example 1 0.46 mg (1.24 μmo) of allyl palladium chloride dimer
l, 2.5 μmol as palladium), (R)-(+)
-2-diphenylphosphino-2'-methoxy-1,1
′ -Binaphtyl 2.34 mg (5 μmol), norbornene
2.354 g (25 mmol) and trichlorosilane 2.5 m
1 (25 mmol) was mixed under ice cooling and the mixture was stirred for 12 hours as it was. Then, the reaction mixture was distilled under reduced pressure to 1.0 Torr.
r, 5.48 by collecting the fraction when heated to 100 ℃
g of (1S, 2S, 4R) -2-trichlorosilylnorbornane was obtained. The isolation yield was 95.5%.

The optical purity of the product was determined by converting the silyl group into a hydroxyl group while maintaining the configuration by the following method.
As dinitrophenyl carbamate, it was determined by performing HPLC analysis on a column for separating optical isomers.

5.48 g of (1S, 2 obtained by distillation
S, 4R) -2-Trichlorosilylnorbornane was added dropwise to a diethyl ether solution (400 ml) of 5 ml of ethanol and 10 ml of triethylamine at room temperature, and the mixture was stirred for 5 hours. The reaction solution was filtered through Celite, the filtrate was concentrated under reduced pressure, and the residue was isolated and purified by distillation under reduced pressure (1S, 2S,
4R) -2-Triethoxysilylnorbornane 5.56 g
(86% yield from norbornene) was obtained. This thing 516
mg (2.0 mmol) to potassium bicarbonate 400 mg (2.0
(mmol) in a mixed solution of 8 ml of THF and 8 ml of methanol at room temperature, 1.5 ml of 30% aqueous hydrogen peroxide was further added, and the mixture was stirred at 50 ° C. overnight. The reaction mixture was allowed to cool to room temperature, diluted with 30 ml of diethyl ether, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The crude product was purified by distillation with a Kugelrohr distillation apparatus to obtain 162 mg of ex
O-norborneol was obtained (yield 72%).

[0042]

[Chemical 17]

¹ H-NMR (δ value (ppm) in CDCl ₃ ) 0.9 to 1.7
(m, 9H), 2.1 (d, J = 4.4Hz, 1H), 2.3 (s, 1H), 3.8 (d, J = 6.
(8 Hz, 1H) The exo-norborneol thus obtained was heated to 50 ° C. with 3,5-dinitrophenylisocyanate in benzene in the presence of pyridine to give dinitrophenylcarbamate, which was used as a column for separating optical isomers (Sumitomo Chemical OA-
4500, eluent: hexane / dichloroethane / ethanol = 50/15/1) and HPLC analysis was carried out to find an optical purity of 93% ee.

Example 2 0.92 mg (2.5 μmo) of allyl palladium chloride dimer
l, 5 μmol as palladium), (R)-(+)-
2-diphenylphosphino-2'-methoxy-1,1 '
-Binaphtyl 4.68 mg (10 μmol), bicyclo [2.
2.2] Octene 270 mg (2.5 mmol) and trichlorosilane 0.25 ml (2.5 mmol) were mixed under ice cooling, and the mixture was stirred for 12 hours as it was. The reaction mixture was distilled under reduced pressure to give 514 mg of 2-trichlorosilylbicyclo [2.
2.2] Octene was obtained. The isolation yield was 84.4%, and the optical purity was 91% ee. (The optical purity was measured by the same chemical conversion as in Example 1 through bicyclo [2.2.2] octane-2-ol and dinitrophenylcarbamate. And determined by HPLC analysis).

Bicyclo [2.2.2] octane-2-ol

[0046]

[Chemical 18]

¹ H-NMR (δ value (ppm) in CDCl ₃ ) 1.3 to 1.7
(m, 11H), 1.8 to 2.1 (m, 2H), 3.9 to 4.0 (dm, J = 11Hz, 1H) Example 3 Allyl palladium chloride dimer 0.92 mg (2.5 μmo
l, 5 μmol as palladium), (R)-(+)-
2-diphenylphosphino-2'-methoxy-1,1 '
-Binaphthyl 4.68 mg (10 μmol), norbornadiene 230 mg (2.5 mmol) and trichlorosilane 0.2
5 ml (2.5 mmol) was mixed under ice cooling, and the mixture was stirred for 12 hours as it was. The reaction mixture was distilled under reduced pressure to give 512 mg of 5-
Trichlorosilyl norbornene was obtained. Isolation yield
The optical purity was 90% and 94.7% ee (the optical purity was measured by HPLC analysis using 5-exo-hydroxynorbornene as dinitrophenylcarbamate by the same chemical conversion as in Example 1).

Dinitrophenyl carbamate derivative ¹ H-NMR (δ value (ppm) in CDCl ₃ ) 1.3 to 1.87 (m, 4H), 2.9 (b
rs, 1H), 3.0 (brs, 1H), 4.8 (d, J = 6.8Hz, 1H), 6.0 (m, 1
H), 6.3 (m, 1H), 7.2 (brs, 1H), 8.7 (brs, 3H) Example 4 0.92 mg (2.5 μmo) of allyl palladium chloride dimer
l, 5 μmol as palladium), (R)-(+)-
2-diphenylphosphino-2'-methoxy-1,1 '
-Binaphtyl 4.68 mg (10 μmol), norbornene 23
5 mg (2.5 mmol) and methyldichlorosilane 0.
Mix 31 ml (3.0 mmol) under ice cooling and mix at 0-20 ℃ for 24 hours.
Stir for hours. The reaction mixture was distilled under reduced pressure to give 320 mg of e.
Xo-2-methyldichlorosilyl norbornane was obtained. The isolation yield was 62% and the optical purity was 42% ee (the optical purity was measured by the same chemical conversion as in Example 1 as dinitrophenylcarbamate by HPLC analysis).

Example 5 Zeise salt (K [PtCl ₃ (CH ₂ ═CH
₂ )]) and (R)-(+)-2-diphenylphosphino-2'-methoxy-1,1'-binaphthyl prepared dichloroplatinum ethylene complex 1.9 mg (2.5 μmol),
235 mg (2.5 mmol) of norbornene and 0.31 ml (3.0 mmol) of methyldichlorosilane were mixed under ice cooling and stirred at 0 to 20 ° C for 24 hours. The reaction mixture was distilled under reduced pressure to give 441 mg of exo-2-methyldichlorosilyl norbornane. Isolation yield 85%, optical purity
It was 13% ee (the optical purity was measured by the same chemical conversion as in Example 1 to obtain H as dinitrophenyl carbamate.
This was done by PLC analysis).

[0050]

INDUSTRIAL APPLICABILITY The present invention relates to bicyclo [2.2. n] -based olefin compound by asymmetric hydrosilylation reaction, which can be easily converted into various optically active compounds.
2. It is an industrially excellent method capable of efficiently producing an [n] type silyl compound.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI Technical display location C07F 7/18 B 8018-4H C 8018-4H E 8018-4H L 8018-4H

Claims (5)

[Claims] 1. A compound represented by the general formula (I): (In the formula, n represents 1 or 2, R ¹ and R ² each independently represents a hydrogen atom, an alkyl group, an aralkyl group, an aryl group, an alkoxycarbonyl group, a cyano group or a nitro group, and Represents a single bond or a double bond) with a transition metal catalyst and a structural formula (II): In the presence of an optically active phosphine compound represented by the general formula (III): (In the formula, X, Y and Z each independently represent a hydrogen atom, an alkyl group, an alkoxyl group or a halogen atom), a silane represented by the general formula (IV): 5] Where n, R ¹ , R ² and the line Are the same as above). n] A method for producing an optically active silyl compound. 2. The production method according to claim 1, wherein a palladium compound or a platinum compound is used as the transition metal catalyst. 3. The method according to claim 1, wherein trichlorosilane is used as the silane. 4. The method according to claim 1, 2 or 3, wherein allyl palladium chloride dimer is used as the transition metal catalyst. 5. The method according to claim 1, 2, 3 or 4, wherein an optically active silylnorbornane is produced by using norbornene as the compound represented by the structural formula (I).