JP2011102282A - Optically active cyanohydrin compounds and process for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an optically active cyanohydrin compound and a process for producing the same. <P>SOLUTION: The optically active cyanohydrin compound is represented by formula (1) (wherein R<SB>1</SB>is a linear alkyl group which may have a branch; a cyclic alkyl group which may have a substituent, a linear alkenyl group which may have a branch, a cyclic alkenyl group which may have a substituent, an aryl group which may have a substituent or a heterocycle which may have a substituent; R<SB>2</SB>is hydrogen, an alkali metal, a hydrocarbon group which may have a substituent or a silyl group which may have a substituent; R<SB>3</SB>is an alkyl group, an alkenyl group, allyl group or an aryl group; and R<SB>1</SB>and R<SB>3</SB>may be linked to form a lactone). <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to optically active cyanohydrin compounds and a method for producing the same.

  Cyanohydrins are key intermediates in the synthesis of useful substances such as optically active α-hydroxycarboxylic acids, α-hydroxyaldehydes, and β-aminoalcohols. One typical synthesis method is an asymmetric cyanation reaction of aldehydes and ketones, and trimethylsilyl cyanide, which is easily available, is generally used as a reactant. In cyanosilylation, studies using catalytic amounts of chiral Lewis acids and Lewis bases have been made (J. Chem. Soc. Chem. Commun., 1973, p55-56 and Chem. Ber., 1973, 106, p587-593). High enantioselectivity has also been reported. Furthermore, the present inventors have already proposed to use a lithium salt or the like as a catalyst for the cyanosilylation reaction (see JP-A-2006-219457).

  However, in the case of the techniques described in J. Chem. Soc. Chem. Commun., 1973, p55-56 and Chem. Ber., 1973, 106, p587-593, expressed in large quantities ((substrate / catalyst)). A catalyst having a ratio of 1 to 100), the preparation of the catalyst is complicated, the catalyst is unstable, it is necessary to use an excess amount of a trialkylsilyl cyanide compound relative to the carbonyl compound, after the reaction There are problems such as complicated post-processing.

  In the case of the technique described in JP-A-2006-219457, the preparation of the catalyst is easy and the stability of the catalyst is excellent, but there is a problem that an optically active product having high enantioselectivity cannot be obtained. is there. That is, in this technique, since only an achiral salt such as LiCl is used as a catalyst, all products are racemic (ie, 0% ee).

  Therefore, as a result of intensive studies to solve the above-mentioned conventional problems, the present inventors have produced a cyanation catalyst that is easy to prepare a catalyst, has high catalyst stability, and can obtain an optically active cyanohydrin compound. Succeeded, and filed a patent application prior to the present application (see WO2008-099965A1). However, in this technical field, it is desired to produce optically active cyanohydrin compounds having various structures.

JP 2006-219457 WO2008-099965A1

J. Chem. Soc. Chem. Commun., 1973, p55-56 and Chem. Ber., 1973, 106, p587-593

  An object of the present invention is to solve the above conventional problems and provide an optically active cyanohydrin compound and a method for producing the same.

As a result of intensive studies on a substrate for obtaining an optically active cyanohydrin compound, the present inventors have found that an optically active cyanohydrin compound can be obtained by using a ketoester compound represented by the following general formula (3). I found it.
That is, one embodiment of the present invention is an optically active cyanohydrin compound represented by the following general formula (1).

In general formula (1), R ₁ is a chain alkyl group which may have a branch, a cyclic alkyl group which may have a substituent, a chain alkenyl group which may have a branch, a substituent. The cyclic alkenyl group which may have a group, the aryl group which may have a substituent, or the heterocyclic ring which may have a substituent is shown. R ₂ represents a hydrogen atom, an alkali metal, a hydrocarbon group which may have a substituent, or a silyl group which may have a substituent. R ₃ represents an alkyl group, an alkenyl group, an allyl group, or an aryl group. R ₁ and R ₃ may be bonded to form a lactone.
A preferred embodiment of the present invention is an optically active cyanohydrin compound in which R ₂ in the general formula (1) is a hydrogen atom.
Another preferred embodiment of the present invention is an optically active cyanohydrin compound in which R ₂ in the general formula (1) is trimethylsilyl (TMS).
Another embodiment of the present invention is:

In the presence of a cyanation catalyst represented by the following general formula (2),
(In the general formula (2), R _{4 to} R ₇ may be the same or different, and each may be a hydrocarbon group which may have a substituent, and R ₄ and R ₅ and / or R _6. And R ₇ may form an optionally substituted carbon chain ring; R _{8 to} R ₁₁ may be the same or different, and each may have a hydrogen atom or a substituent. A good hydrocarbon group, R ₈ and R ₉ and / or R ₁₀ and R ₁₁ may form an optionally substituted carbon chain ring; R ₁₂ and R ₁₃ may be the same or each Hydrocarbon groups which may be different and each may have a hydrogen atom or a substituent; W, X and Y may be the same or different and each may have a substituent Where X and / or Y may not be present; M represents a metal or metal ion; Each ligand may be arranged how)
The following general formula (3)

(In the general formula (3), R ₁ is a chain alkyl group which may have a branch, a cyclic alkyl group which may have a substituent, a chain alkenyl group which may have a branch, A cyclic alkenyl group which may have a substituent, an aryl group which may have a substituent, or a heterocyclic ring which may have a substituent, R ₃ represents an alkyl group, an alkenyl group, an allyl. A keto ester compound represented by the following general formula (4):

(In General Formula (4), R ₂ represents a hydrogen atom, an alkali metal, a hydrocarbon group which may have a substituent, or a silyl group which may have a substituent.) A method of producing an optically active cyanohydrin compound represented by the above general formula (1), comprising a step of reacting a compound with a compound; and a step of reacting a reaction product obtained in the step with a salt of a metal compound. is there.
Another embodiment of the present invention is:

In the presence of a cyanation catalyst obtained by reacting a cyanation catalyst represented by the following general formula (2) with a salt of a metal compound,
(In the general formula (2), R _{4 to} R ₇ may be the same or different, and each may be a hydrocarbon group which may have a substituent, and R ₄ and R ₅ and / or R _6. And R ₇ may form an optionally substituted carbon chain ring; R _{8 to} R ₁₁ may be the same or different, and each may have a hydrogen atom or a substituent. A good hydrocarbon group, R ₈ and R ₉ and / or R ₁₀ and R ₁₁ may form an optionally substituted carbon chain ring; R ₁₂ and R ₁₃ may be the same or each Hydrocarbon groups which may be different and each may have a hydrogen atom or a substituent; W, X and Y may be the same or different and each may have a substituent Where X and / or Y may not be present; M represents a metal or metal ion; Each ligand may be arranged how)
The following general formula (3)

(In the general formula (3), R ₁ is a chain alkyl group which may have a branch, a cyclic alkyl group which may have a substituent, a chain alkenyl group which may have a branch, A cyclic alkenyl group which may have a substituent, an aryl group which may have a substituent, or a heterocyclic ring which may have a substituent, R ₃ represents an alkyl group, an alkenyl group, an allyl. A group or an aryl group.)
A ketoester compound represented by the following general formula (4):

(In General Formula (4), R ₂ represents a hydrogen atom, an alkali metal, a hydrocarbon group which may have a substituent, or a silyl group which may have a substituent.)
A process for producing an optically active cyanohydrin compound represented by the above general formula (1), which comprises a step of reacting with a cyanide compound represented by formula (1).
A preferred embodiment of the present invention is a method for producing an optically active cyanohydrin compound represented by the above general formula (1), wherein M in the above general formula (2) is divalent ruthenium.
Another preferred embodiment of the present invention is an optical system represented by the general formula (1), wherein W in the general formula (2) is a 1,1′-binaphthyl group or a 1,1′-biphenyl group. It is a manufacturing method of an active cyanohydrin compound.

  According to a preferred embodiment of the present invention, an optically active cyanohydrin compound is obtained.

Hereinafter, the present invention will be described in detail.
One embodiment of the present invention is an optically active cyanohydrin compound represented by the general formula (1). First, the cyanation catalyst used in the method for producing the optically active cyanohydrin compound represented by the general formula (1) will be described.
In the present invention, a cyanation catalyst represented by the following general formula (2) may be used, or a cyanation catalyst represented by the general formula (2) is used as the first catalyst, and the second catalyst is used. Alternatively, a metal compound salt may be used, and a cyanation catalyst obtained by reacting these may be used. These cyanation catalysts are suitably used as a catalyst for producing the optically active cyanohydrin compound of the present invention. Hereinafter, the first catalyst and the second catalyst will be described in this order, and a method for producing an optically active cyanohydrin compound using these will be described.
<First catalyst>
The first catalyst has the general formula (2)

It is represented by
In the general formula (2), R _{4 to} R ₇ may be the same or different from each other, and each is a hydrocarbon group which may have a substituent, and R ₄ and R ₅ and / or R ₆ And R ₇ may form a carbon chain ring which may have a substituent.
Specific examples of R _{4 to} R ₇ include hydrocarbon groups such as alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, and phenylalkyl. In particular, a phenyl group, a tolyl group, and a xylyl group are preferable as R _{4 to} R ₇ . Specific examples of the substituent that R _{4 to} R ₇ have include a hydrogen atom, alkyl, alkenyl, cycloalkyl, aryl, alkoxy, ester, acyloxy, halogen atom, nitro, cyano group, and the like. It may have various substituents. In particular, a hydrogen atom, a p-methyl group, and a 3,5-dimethyl group are preferable as a substituent.

When R ₄ and R ₅ (or R ₆ and R ₇ ) form a carbon chain ring, alkyl, alkenyl, aryl, cycloalkyl, alkoxy, ester, acyloxy, halogen atom, nitro, cyano on this carbon chain Those in which various permissible substituents such as a group are substituted may be used. R _{4 to} R ₇ are preferably a phenyl, p-tolyl, m-tolyl, 3,5-xylyl, p-tert-butylphenyl, p-methoxyphenyl, cyclopentyl, or cyclohexyl group.

R _{8 to} R ₁₁ may be the same or different and each is a hydrocarbon group optionally having a hydrogen atom or a substituent, and R ₈ and R ₉ and / or R ₁₀ and R ₁₁ are You may form the carbon chain ring which may have a substituent.
Specific examples of R _{8 to} R ₁₁ are preferably a hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and aryl group. In particular, as R _{8 to} R ₁₁ , R ₈ and R ₁₀ are preferably hydrogen atoms, and R ₉ and R ₁₁ are preferably phenyl groups.
Specific examples of the substituent that R _{8 to} R ₁₁ have include various permissible substituents such as alkyl, alkenyl, cycloalkyl, aryl, alkoxy, ester, acyloxy, halogen atom, nitro, and cyano group. In particular, a hydrogen atom, a methyl group, or a methoxy group is preferable as a substituent.

When R ₈ and R ₉ (or R ₁₀ and R ₁₁ ) form a carbon chain ring, alkyl, alkenyl, aryl, cycloalkyl, alkoxy, ester, acyloxy, halogen atom, nitro, cyano on this carbon chain Those in which various permissible substituents such as a group are substituted may be used. As R ₈ ~R _11, R ₈ and R ₁₀ are hydrogen atoms, it is preferred that R ₉ and R ₁₁ is a phenyl group.

R ₁₂ and R ₁₃ may be the same or different, and each is a hydrogen atom or a hydrocarbon group optionally having a substituent.
Specific examples of R ₁₂ and R ₁₃ include hydrocarbon groups such as a hydrogen atom, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, and phenylalkyl. In particular, hydrogen atoms are preferable as R ₁₂ and R ₁₃ . Specific examples of the substituent that R ₁₂ and R ₁₃ have include various permissible substituents such as alkyl, alkenyl, cycloalkyl, aryl, alkoxy, ester, acyloxy, halogen atom, nitro, cyano group and the like. In particular, a hydrogen atom, a methyl group, or a methoxy group is preferable as a substituent.

In the general formula (2), the W bond chain is a divalent hydrocarbon chain (for example, —CH ₂ —, — (CH ₂ ) ₂ —, — (CH ₂ ) ₃ —, — (CH ₂ ) ₄ —. Linear hydrocarbon chains such as —CH ₂ CH (CH ₃ ) —, —CH (CH ₃ ) CH (CH ₃ ) —and other branched hydrocarbon chains; —C ₆ H ₄ —, —C ₆ And cyclic hydrocarbons such as H _10- ), bivalent binaphthyl, divalent biphenyl, divalent paracyclophane, divalent bipyridine, divalent cyclic heterocycle and the like. Among these, a 1,1′-binaphthyl group or a 1,1′-biphenyl group, which may have a substituent and in which the 2-position or 2′-position is bonded to phosphine, is preferable. In addition, these bonding chains may have various permissible substituents such as alkyl, alkenyl, cycloalkyl, aryl, alkoxy, ester, acyloxy, halogen atom, nitro, cyano group, It may be bonded via a carbon atom, oxygen atom, nitrogen atom, sulfur atom or the like. W preferably has optical activity. For example, when W contains a 1,1′-binaphthyl group, it is preferably (R) -1,1′-binaphthyl group or (S) -1,1′-binaphthyl group, When it contains 1′-biphenyl group, it is preferably (R) -1,1′-biphenyl group or (S) -1,1′-biphenyl group.

In addition, since the diphosphine derivative (R ₁ R ₂ P—W—PR ₃ R ₄ ), which is a bidentate ligand containing W, is coordinated to M, as a preferred specific example of W, this diphosphine derivative is Illustrate. That is, as diphosphine derivatives, BINAP (2,2′-bis (diphenylphosphino) -1,1′-binaphthyl), TolBINAP (2,2′-bis [(4-methylphenyl) phosphino] -1,1 ′ -Binaphthyl), XylBINAP (2,2'-bis [(3,5-dimethylphenyl) phosphino] -1,1'-binaphthyl), 2,2'-bis [(4-t-butylphenyl) phosphino]- 1,1′-binaphthyl, 2,2′-bis [(4-isopropylphenyl) phosphino] -1,1′-binaphthyl, 2,2′-bis [(naphthalen-1-yl) phosphino] -1,1 '-Binaphthyl, 2,2'-bis [(naphthalen-2-yl) phosphino] -1,1'-binaphthyl, BICHEMP (2,2'-bis (dicyclohexylphosphino) -6,6'-dimethyl-1 , 1'-biphenyl), BPPFA (1- [1,2-bis- (diphenylphosphino) ferrocenyl] Tilamine), CHIRAPHOS (2,3-bis (diphenylphosphino) butane), CYCPHOS (1-cyclohexyl-1,2-bis (diphenylphosphino) ethane), DEGPHOS (1-substituted-3,4-bis (diphenyl) Phosphino) pyrrolidine), DIOP (2,3-isopropylidene-2,3-dihydroxy-1,4-bis (diphenylphosphino) butane), SKEWPHOS (2,4-bis (diphenylphosphino) pentane), DuPHOS (Substituted-1,2-bis (phosphorano) benzene), DIPAMP (1,2-bis [(o-methoxyphenyl) phenylphosphino] ethane) NORPHOS (5,6-bis (diphenylphosphino) -2-norbornene ), PROPHOS (1,2-bis (diphenylphosphino) propane), PHANEPHOS (4,12-bis (diphenylphosphino)-[2,2 ′]-paracyclophane), substituted-2,2′-bis Diphenylphosphino) -1,1′-bipyridine, SEGPHOS ((4,4′-bi-1,3-benzodioxole) -5,5′-diyl-bis (diphenylphosphino)), BIFAP (2 , 2′-bis (diphenylphosphanyl) -1,1′-bidibenzofuranyl) and the like.
In particular, the diphosphine derivatives are BINAP (2,2′-bis (diphenylphosphino) -1,1′-binaphthyl), TolBINAP (2,2′-bis [(4-methylphenyl) phosphino] -1,1 ′. -Binaphthyl) and XylBINAP (2,2′-bis [(3,5-dimethylphenyl) phosphino] -1,1′-binaphthyl) are preferred.

X and Y in the general formula (2) are the same or different from each other, and each is a bonding chain that may have a substituent. However, X and / or Y may not be present.
Specific examples of X and Y include divalent hydrocarbon chains (eg, straight chain such as —CH ₂ —, — (CH ₂ ) ₂ —, — (CH ₂ ) ₃ —, — (CH ₂ ) ₄ —, etc. Hydrocarbon chain having branches such as —CH ₂ CH (CH ₃ ) —, —CH (CH ₃ ) CH (CH ₃ ) —; —C ₆ H ₄ —, —C ₆ H ₁₀ — and the like And a divalent heterocyclic ring, a hetero atom, an alkyl chain containing a hetero atom, and the like.
The case where X and / or Y does not exist means a case where C = and C (R ₅ ) R ₆ are directly bonded, for example, as in the compound of the following general formula (II). .

M in the general formula (2) represents a metal or a metal ion. Specific examples of M include Ru, Fe, Pd, Rh, and Co. In particular, M is preferably divalent ruthenium.
In general formula (2), the fact that each ligand of M may be arranged means that the positions of N, P, O, and O bonded to M are arbitrary. . For example, in the formula (I), O and O face each other across M, but, for example, an arrangement in which O and N and O and P face each other may be used.
Specific examples of the first catalyst include, for example, the general formula (II)

(Ru [(S) -phenylglycine] ₂ [(S) -binap]).
Examples of the method for producing the first catalyst include the method described in WO2008-099965A1.

<Second catalyst>
The second catalyst is a salt of a metal compound, and is preferably selected from one or more salts selected from the group of lithium, sodium, potassium, cesium, magnesium and lanthanoids, and / or ammonium salts. The second catalyst is a cocatalyst of the first catalyst.
Examples of the lithium salt include LiOR (R: alkyl, alkenyl or aryl), LiR (R: alkyl, alkenyl or aryl), lithium halide (LiF, LiCl, LiBr, LiI), LiClO ₄ , Li (OTf), Li (OAc), LiCN, Li ₂ CO _{3 and the} like can be mentioned, but other salts may be used. Further, the lithium salt described in JP-A-2006-219457 can also be used (paragraph 0008 of JP-A-2006-219457). In particular, LiOC ₆ H ₅ , LiCl and LiClO ₄ are preferable.
As the salt of sodium, potassium, and cesium, those corresponding to the lithium salt described above can be used. Magnesium salts include magnesium triflate, and lanthanoid salts include ytterbium triflate. Examples of the ammonium salt include organic ammonium salts such as tetrabutylammonium chloride.
In one embodiment of the cyanation catalyst that can be used in the present invention, since an optically active complex (first catalyst) is also used as a catalyst in addition to an achiral salt (second catalyst), an optically active product is obtained. be able to. On the other hand, when only an achiral salt such as LiCl is used as a catalyst (for example, a catalyst described in JP-A-2006-219457), all products are racemic (ie, 0% ee).
That is, when only an achiral salt such as LiCl is used as a catalyst, an achiral reaction occurs, but an asymmetric reaction can be caused in the present invention.

<Method for producing optically active cyanohydrin compound>
In another embodiment of the present invention, a ketoester compound represented by the general formula (3) and a cyanide compound represented by R ₂ CN (general formula (4)) are present in the presence of the first catalyst. This is a method for producing an optically active cyanohydrin compound represented by the following general formula (1), which comprises a step of reacting and a step of adding a second catalyst to the reaction product obtained in this step. Furthermore, another embodiment of the present invention provides a keto ester compound represented by the above general formula (3) in the presence of a catalyst obtained by reacting a first catalyst and a second catalyst, and the above general formula ( 4) A method for producing an optically active cyanohydrin compound represented by the following general formula (1), which comprises a step of reacting with a cyanide compound represented by 4).

In general formula (1), R ₁ is a chain alkyl group which may have a branch, a cyclic alkyl group which may have a substituent, a chain alkenyl group which may have a branch, a substituent. The cyclic alkenyl group which may have a group, the aryl group which may have a substituent, or the heterocyclic ring which may have a substituent is shown. R ₂ represents a hydrogen atom, an alkali metal, a hydrocarbon group which may have a substituent, or a silyl group which may have a substituent. R ₃ represents an alkyl group, an alkenyl group, an allyl group, or an aryl group. R ₁ and R ₃ may be bonded to form a lactone.

The cyclic alkyl group, cyclic alkenyl group, aryl group, or heterocyclic ring in R ₁ is further various permissible substituents such as alkyl, alkenyl, cycloalkyl, aryl, alkoxy, ester, acyloxy, halogen atom, nitro, cyano and the like. You may have.
Examples of the chain alkyl group for R ₁ include those having no branch such as methyl, ethyl, propyl, and n-butyl, and those having a branch such as isopropyl and sec-butyl.
Examples of the cyclic alkyl group for R ₁ include cyclopentyl and cyclohexyl.
Examples of the alkenyl group for R ₁ include an ethenyl group, a propenyl group, a butenyl group, and a propenyl group.
Examples of the aryl group for R ₁ include phenyl, tolyl, xylyl, naphthyl and the like.
Examples of the heterocyclic ring in R ₁ include those having a 5-membered ring skeleton such as pyrrole, thiophene, furan, pyrazole, imidazole, thiazole, and oxazole, and those having a 6-membered ring skeleton such as pyridine, pyrimidine, and pyridazine. .

Examples of the alkyl group for R ₃ include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl and the like.
Examples of the alkenyl group for R ₃ include an ethenyl group, a propenyl group, a butenyl group, and a propenyl group.
Examples of the aryl group for R ₃ include phenyl, tolyl, xylyl, naphthyl and the like.

Examples of the alkali metal in R ₂ include Li, Na, K, and the like.
Examples of the hydrocarbon group for R ₂ include aliphatic, alicyclic saturated or unsaturated hydrocarbon groups, monocyclic aromatic or araliphatic hydrocarbons, polycyclic aromatic or araliphatic hydrocarbons. Etc. Further, these hydrocarbon groups may further have various permissible substituents such as alkyl, alkenyl, cycloalkyl, aryl, alkoxy, ester, acyloxy, halogen atom, nitro, cyano and the like. Further, the silyl group in R ₂ may further have various permissible substituents such as alkyl, alkenyl, cycloalkyl, aryl, alkoxy, ester, acyloxy, halogen atom, nitro, cyano and the like.
Specific examples of the hydrocarbon group include alkyl, alkenyl, cycloalkyl, cycloalkenyl, phenyl, tolyl, xylyl, naphthyl, phenylalkyl and the like.
Specific examples of the silyl group include trimethylsilyl, di-t-butylmethylsilyl, diphenyl-t-butylsilyl and the like.

As the ketoester compound which is a substrate, a compound represented by the following general formula (3) (wherein R ₁ and R ₃ have the same meaning as in general formula (1)) can be used.
Representative examples of the ketoester compound as a substrate include the following compounds, but are not limited thereto.

The cyanide compound, (wherein, R ₂ is Formula (1) as synonymous) R ₂ CN can be used.
In addition, as the cyanide compound (R ₂ CN) that is a raw material, NaCN, KCN, or the like can be used. Accordingly, in this case, R ₂ may be an alkali metal such as Na or K.

  The molar ratio S / C of the ketoester compound to the cyanation catalyst in the present invention (S is a ketoester compound as a substrate, and C is a catalyst) is preferably 1 to 1,000,000, and more preferably 1 to 100,000. Further, the molar ratio of the cyanide compound to the ketoester compound is preferably 1 to 3, and more preferably 1 to 1.3.

The cyanation reaction for producing the cyanohydrin compound is preferably performed at normal pressure under an inert atmosphere such as argon.
Further, the cyanation reaction proceeds even in the absence of a solvent or in a reaction solvent. Examples of the reaction solvent include aromatic hydrocarbon solvents such as toluene and xylene, aliphatic hydrocarbon solvents such as pentane and hexane, halogen-containing hydrocarbon solvents such as methylene chloride, ethers such as t-butyl methyl ether and tetrahydrofuran (THF). Examples thereof include solvents containing heteroatoms such as system solvents, acetonitrile, N, N-dimethylacetamide (DMA), N, N-dimethylformamide (DMF), N-methylpyrrolidone, dimethylsulfoxide (DMSO) and the like. In addition, when the cyanation catalyst in this invention is dissolved and used for reaction, the same solvent as mentioned above can be used.

Although reaction temperature is not specifically limited, -78-50 degreeC is preferable and -70-40 degreeC is more preferable. The reaction time varies depending on the type of substrate, but in many cases it is in the range of 1 minute to 12 hours. As a method for collecting the cyanohydrin compound from the reaction mixture after completion of the reaction, distillation or extraction may be employed.
A cyanohydrin compound can be produced by reacting a ketoester compound with a cyanide compound in the presence of the above-described cyanation catalyst. Specifically, for example, a catalyst solution obtained by dissolving a cyanation catalyst in an organic solvent or a solid matter of a cyanation catalyst (catalyst solid matter) is added to a container containing a ketoester compound and a cyanide compound and stirred. Thus, the ketoester compound and the cyanide compound can be reacted.
Here, when the ketoester compound is oily, the catalyst solution or the catalyst solid may be added and reacted in a solventless container containing the ketoester compound and the cyanide compound. When the ketoester compound is a solid, the catalyst solution or the catalyst solid may be added to the container containing the ketoester compound, the cyanide compound, and the reaction solvent for reaction.

EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to these Examples.
(A) Analysis method (i) Gas chromatography (GC) analysis was performed with a Shimadzu GC-17A or GC-2010 apparatus using helium carrier gas.
(Ii) NMR spectra were obtained with a JEOL JNM-EX270 or JNM-A400 spectrometer.
(Iii) Carbon multiplicity was measured by DEPT experiment.
(Iv) IR spectrum was recorded with JASCO FT / IR-4100 spectrophotometer.
(V) The optical rotation was measured with a JASCO DIP-360 polarimeter.
(Vi) Silica gel column chromatography was performed on silica gel 60N (63 to 210 μm; Kanto Chemical Co., Inc.).
(Vii) Preparative thin layer chromatography was performed on Merck silica gel 60PF ₂₅₄ (Merck Ltd).
(Viii) Mass spectrometric measurement was performed at the Hokkaido University Instrument Analysis Center.

(B) Preparation of starting material Ketoesters 1a and 1b represented by the following structural formulas are commercially available. Other ketoesters were synthesized by known methods.

A ruthenium complex (S, S, S) -3a represented by the following structural formula (where Ar = C ₆ H ₅ ) was prepared by a conventionally reported method.

Ruthenium complex represented by the above structural formula (where Ar = 3,5- (CH ₃ ) ₂ C ₆ H ₃ ): Ru [(S) -phenylglycine] ₂ [(S) -xylyl-binap] [(S , S, S) -3b] was synthesized as follows.
A dry 100 mL Schlenk tube connected to a supply system of argon (99.99% purity) (all equipment was dried in an oven at 55 ° C. prior to use) was added to Teflon (Teflon). ) A coated magnetic stir bar and glass stopper were attached. [RuCl ₂ (benzene)] ₂ (obtained from Aldrich Co.) (90 mg, 0.18 mmol) and (S) -xylyl-BINAP (obtained from Strem Chemicals, Inc.) (250 mg, 0.34 mmol) The gas layer was replaced with argon. N, N-dimethylformamide (DMF) (anhydrous DMF (99.5% purity) was obtained from Kanto Chemical Co., Inc. and degassed by three freeze-thaw cycles before use) with a syringe in an argon atmosphere) ( 6 mL) was introduced. The reddish brown suspension was stirred at 100 ° C. for 10 minutes, and the resulting clear reddish brown solution containing the BINAP-Ru (II) complex was cooled to 25 ° C.

In a separate 50 mL Schlenk tube, sodium (S) -phenylglycinate (obtained from Acros Co.) (205 mg, 1.18 mmol) and methanol (anhydrous methanol (99.9% purity) from Kanto Chemical Co., Inc.) (Acquired) (10 mL) was added and the solution was degassed for 3 freeze-thaw cycles. Under an argon atmosphere, this was transferred to the DMF solution of the above BINAP-Ru (II) complex with a syringe, and the resulting pale red solution was stirred at 25 ° C. for 12 hours. With vigorous stirring, water (30 mL) was added to the solution to precipitate a yellowish orange solid. After filtration, the collected solid was dissolved in ethyl acetate (50 mL). The solution was washed with 3 portions of 50 mL of water, then with 50 ml of saturated brine, and dried over MgSO ₄ . After filtration through a celite pad, the solution was concentrated under reduced pressure (0.4 mmHg) to give a yellowish orange solid. The crude product was purified by preparative TLC (silica gel, eluent; ethyl acetate). The resulting yellow solid was reprecipitated with a mixture of Et ₂ O (5 mL) and pentane (95 mL), then filtered and dried under reduced pressure to obtain ruthenium complex (S, S, S) -3b as a pale salt. Obtained as a yellow powder (255 mg, 66% yield); ¹ H NMR (400 MHz, CDCl ₃ ): δ = 1.80 (s, 12H, CH ₃ of xylyl moiety), 2.23 (brs, 2H, NHH), 2.42 (s, 12H, CH ₃ of xylyl moiety), 3.17 (brs, 2H, NHH), 3.70 (t, 2H, J = 7.8 Hz, 2PhCH), 5.95 (s, 2H, aromatic H), 6.24 (d, 2H , J = 8.8 Hz, aromatic H), 6.66 (brs, 4H, aromatic H), 6.72 (m, 4H, aromatic H), 6.80 (m, 2H, aromatic H), 7.107.19 (m, 10H, aromatic H ), 7.407.85 ppm (m, 8H, aromatic H), 8.13 (m, 2H, aromatic H); ³¹ P NMR (161.7 MHz, CDCl ₃ ): δ = 52.3 ppm (s); ESI-MS: m / z calcd for C ₆₈ H ₆₄ N ₂ O ₄ P ₂ Ru: 1136.34 ([M] ⁺ ); found: 1136.33.

(C) General Procedure for Asymmetric Cyanosilylation (S / C = 1,000) Cyanosilylation of methylbenzoylformate (1a) was performed as shown in the following reaction formula.
Ruthenium complex (S, S, S) -3a (5.1 mg, 5.0 mmol) was added to a 500 mL Schlenk flask equipped with a Teflon-coated magnetic stir bar. The air in the Schlenk flask was replaced with argon (99.99% purity). t-C ₄ (obtain anhydrous tBuOMe (99.5% purity) from Kanto Chemical Co., _{Ltd.) H 9 OCH 3 (50mL)} , methyl benzoyl formate (1a) (0.82g, 5.0 mmol) and C ₆ Schlenk H ₅ OLi (Li ₂ CO ₃ obtained from Aldrich Co., Ltd.) (50 μL, 1.0 mmol) in 100 mM THF solution (THF (99.5% purity) obtained from Kanto Chemical Co., Inc.) Added to the flask and the mixture was stirred for 30 minutes. The resulting yellow solution was cooled to -60 ° C. Then (CH _{3) 3} SiCN (obtained from Wako Pure Chemical Industries, Ltd. to (CH _{3) 3} SiCN, and purified by distillation before use) (0.99 g, 10.0 mmol) dropwise over 15 minutes And the mixture was stirred for 18 hours. After evaporating the solvent and volatile compounds at ambient temperature under reduced pressure, the residue was suspended in hexane (100 mL). The suspension was filtered through a celite pad and concentrated at ambient temperature under reduced pressure. The residue was purified by simple distillation to obtain the following compound number 2a (1.27 g, yield: 97%, optical purity: 99% ee) as a colorless oil.

Boiling point: 116-119 ° C./1 mmHg; IR (KBr neat) 2958, 1767, 1451, 1255, 1148, 870, 850 cm ⁻¹ ; ¹ H NMR (400 MHz, CDCl ₃ ): δ 0.26 (s, _{9H, Si (CH 3) 3} ), 3.79 (s, 3H, OCH 3), 7.40-7.45 (m, 3H, aromatic), 7.63-7.67 (m, 2H, Aromatic); ¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.66 (CH ₃ ), 54.0 (CH ₃ ), 74.8 (C), 117.9 (C), 125.5 (CH) , 128.8 (CH), 129.8 (CH), 136.4 (C), 167.5 (C); HRMS (EI ⁺ ), m / z (M ⁺ ) calculated value 263.0978, measured value 263.0970; calcd elemental analysis _{C 13 H 17 NO 3 Si:} C, 5 .29, H, 6.51, N, 5.32. Found: C, 59.23, H, 6.45, N, 5.25; Chiral GC analysis: column, InertCap CHIRAMIX (0.25 mm x 30 m); carrier gas helium (100 kPa): column temperature, 0.5 Temperature rise from 70 ° C to 135 ° C at a rate of ° C / min; minor component t _R , 133.5 minutes (0.5%); major component t _R , 134.7 minutes (99.5%); α] _D ²⁴ 24.00 ° (c 1.127, CH ₃ Cl)

Various optically active cyanohydrin compounds were produced in the same manner as Compound No. 2a except that the starting materials and cyanation catalyst shown below were used and the production conditions shown below were used.

(D) Analytical data of asymmetric cyanosilylation product The analytical data of the optically active cyanohydrin compound produced above is shown below.
(R)-(+)-Methyl 2-cyano-2-phenyl-2-trimethylsilyloxyacetate (Compound No. 2a)
98% yield;
Colorless oil;
116-119 ° C./1 mmHg (bulb-to-bulb);
IR (KBr) 2958, 1767, 1451, 1255, 1198, 1148, 870, 850, cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.26 (s, 9H, Si (CH ₃ ) ₃ ), 3.79 (s, 3H, OCH ₃ ), 7.40-7.45 (m, 3H, Aromatic), 7.63-7.67 (m, 2H, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.66 (CH ₃ ), 54.0 (CH ₃ ), 74.8 (C), 117.9 (C), 125.5 (CH), 128.8 (CH), 129.8 (CH), 136.4 (C), 167.5 (C);
HRMS (EI ⁺ ), m / z (M ⁺ ) calculated 263.0978, found 263.0970;
Elemental analysis: Calculated for _{C 13 H 17 NO 3 Si:} C, 59.29, H, 6.51, N, 5.32. Found: C, 59.23, H, 6.45, N, 5.25;
Chiral GC analysis: column, InertCap CHIRAMIX (0.25 mm × 30 m); carrier gas helium (100 kPa): column temperature, heated from 70 ° C. to 135 ° C. at a rate of 0.5 ° C./min; minor component t _R , 133 0.5 min (0.5%); t _{R of} the main component, 134.7 min (99.5%);
[Α] _D ²⁴ 24.00 ° (c 1.127, CHCl ₃ ), 99% ee.

(+)-Ethyl 2-cyano-2-phenyl-2-trimethylsilyloxyacetate (Compound No. 2b)
97% yield;
Colorless oil;
90-93 ° C./0.9 mmHg (valve / valve);
IR (KBr) 2963, 1763, 1450, 1255, 1195, 1148, 880, 848, cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.27 (s, 9H, Si (CH ₃ ) ₃ ), 1.24 (t, 3H, J = 7.1 Hz, CH ₃ ), 4.16-4. _{31 (m, 2H, CH 2} ), 7.39-7.43 (m, 3H, aromatic), 7.64-7.67 (m, 2H, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.70 (CH ₃ ), 13.8 (CH ₃ ) 63.4 (CH ₂ ), 74.9 (C), 118.0 (C), 125.5 (CH), 128.7 (CH), 129.7 (CH), 136.5 (C), 167.0 (C);
HRMS (EI ⁺ ), m / z (M ⁺ ) calculated value 277.1134, actual value 277.1127;
Chiral GC analysis: column, InertCap CHIRAMIX (0.25 mm × 30 m); carrier gas helium (100 kPa); column temperature, heated from 70 ° C. to 150 ° C. at a rate of 0.6 ° C./min; minor component t _R , 122 7 minutes (6.2%); t _{R of} the main component, 123.6 minutes (93.8%);
[Α] _D ²¹ 15.72 ° (c 1.052, CHCl ₃ ), 87% ee.

(+)-Isopropyl 2-cyano-2-phenyl-2-trimethylsilyloxyacetate (Compound No. 2c)
94% yield;
Colorless oil;
87 ° C./0.1 mmHg (valve / valve);
IR (KBr—neat) 2983, 1759, 1451, 1254, 1195, 1149, 1102, 876, 847 cm ⁻¹ ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.28 (s, 9H, Si (CH ₃ ) ₃ ), 1.15 (d, 3H, J = 6.34 Hz, CH ₃ ), 1.29 (d, _{3H, J = 6.34Hz, CH 3} ), 5.01 ( septet, 1H, J = 6.34Hz, CH ), 7.40-7.42 (m, 3H, aromatic), 7.63- 7.66 (m, 2H, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.77 (CH ₃ ), 21.2 (CH ₃ ), 21.4 (CH ₃ ), 71.7 (CH), 75.0 (C), 118. 1 (C), 125.4 (CH), 128.6 (CH), 129.6 (CH), 136.6 (C), 166.5 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 314.1188, found 314.1184;
Elemental analysis: Calculated value of C ₁₃ H ₁₇ NO ₃ Si: C, 61.82, H, 7.26, N, 4.81. Found: C, 61.80, H, 7.34, N, 4.79;
Chiral GC analysis: column, CP-Chirasil-Dex (0.32 mm × 25 m); carrier gas helium (72 kPa); column temperature, heated from 70 ° C. to 110 ° C. at a rate of 0.3 ° C./min; _R , 117.5 min (25.4%); main component t _R , 119.2 min (74.6%);
[Α] _D ²⁶ 5.95 ° (c 1.061, CHCl ₃ ), 49% ee.

(−)-Tert-butyl 2-cyano-2-phenyl-2-trimethylsilyloxyacetate (Compound No. 2d)
97% yield;
Colorless oil;
125 ° C./0.08 mmHg (valve / valve);
IR (KBr-undiluted) 2979, 1758, 1371, 1255, 1147, 880, 845 cm ^-1;
1 H NMR (400 MHz, CDCl ₃ ): δ 0.28 (s, 9H, Si (CH ₃ ) ₃ ), 1.40 (s, 9H, CH ₃ ), 7.38-7.40 (m, 3H, Aromatic), 7.62-7.64 (m, 2H, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.77 (CH ₃ ), 27.4 (CH ₃ ), 75.1 (C), 84.7 (C), 118.3 (C), 125.4 (CH), 128.5 (CH), 129.4 (CH), 136.8 (C), 165.7 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated value 328.1345, found value 328.1340;
Chiral GC analysis: column, CP-Chirasil-Dex (0.32 mm × 25 m); carrier gas helium (72 kPa); column temperature, heated from 70 ° C. to 120 ° C. at a rate of 0.4 ° C./min; _R , 104.1 min (76.6%); t _{R of} the main component, 105.5 min (23.4%);
[Α] _D ²⁶ -18.81 ° (c 1.092, CHCl ₃ ), 53% ee.
Remaining IR, optical rotation

(+)-Methyl 2-cyano-2- (2-methylphenyl) -2-trimethylsilyloxyacetate (Compound No. 2e)
98% yield;
Colorless oil;
110 ° C./0.1 mmHg (valve / valve);
IR (KBr-undiluted) 2957, 1765, 1254, 1190, 1136, 873, 849 cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.24 (s, 9H, Si (CH ₃ ) ₃ ), 2.39 (s, 3H, CH ₃ ), 3.82 (s, 3H, OCH ₃ ), 7.18-7.32 (m, 3H, aromatic), 7.68 (dd, 1H, J = 1.4, 6.2 Hz, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.73 (CH ₃ ), 19.8 (CH ₃ ) 54.0 (CH ₃ ), 75.5 (C), 117.5 (C), 126.2 (CH), 126.9 (CH), 129.6 (CH), 132.4 (CH), 134.1 (C), 136.2 (C), 167.4 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 300.1026, found 300.1028;
Elemental analysis: Calculated value of C ₁₄ H ₁₉ NO ₃ Si: C, 60.62, H, 6.90, N, 5.05. Found: C, 60.63, H, 6.78, N, 5.02;
Chiral HPLC analysis: column, CHIRALPAK IC; eluent, hexane: 2-propanol = 99: 1; flow rate 0.5 mL / min; column temperature, 40 ° C .; detection, UV 220 nm; minor component t _R , 10.5 min ( 2.8%); main component t _R , 11.3 minutes (97.2%);
[Α] _D ²⁶ 28.92 ° (c 0.998, CHCl ₃ ), 94% ee.

(+)-Methyl 2-cyano-2- (3-methylphenyl) -2-trimethylsilyloxyacetate (Compound No. 2f)
97% yield;
Colorless oil;
95 ° C./0.07 mmHg (valve / valve);
IR (KBr-undiluted) 2957, 1767, 1255, 1167, 1141, 871, 848 cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.26 (s, 9H, Si (CH ₃ ) ₃ ), 2.39 (s, 3H, CH ₃ ), 3.79 (s, 3H, OCH ₃ ), 7.19-7.31 (m, 2H, aromatic), 7.44 (m, 2H, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.72 (CH ₃ ), 21.5 (CH ₃ ) 54.0 (CH ₃ ), 74.9 (C), 118.0 (C), 122.6 (CH), 126.0 (CH), 128.7 (CH), 130.5 (CH), 136.2 (C), 138.7 (C), 167.6 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 300.1026, found 300.1028;
Elemental analysis: Calculated value of C ₁₄ H ₁₉ NO ₃ Si: C, 60.62, H, 6.90, N, 5.05. Found: C, 60.59, H, 6.72, N, 4.96;
Chiral GC analysis: column, CHIRALDEX G-TA (0.25 mm × 30 m); carrier gas helium (100 kPa): column temperature, heating from 50 ° C. to 150 ° C. at a rate of 0.2 ° C./min; minor component t _R 317.4 min (1.5%); main component t _R , 319.8 min (98.5%);
[Α] _D ²⁵ 25.30 ° (c 1.015, CHCl ₃ ), 97% ee.

(+)-Methyl 2-cyano-2- (4-methylphenyl) -2-trimethylsilyloxyacetate (Compound No. 2g)
92% yield;
Colorless oil;
90 ° C./0.09 mmHg (valve / bulb);
IR (KBr-undiluted) 2957, 1767, 1255, 1183, 1148, 874, 849 cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ0.25 (s, 9H, Si (CH ₃ ) ₃ ), 2.37 (s, 3H, CH ₃ ), 3.78 (s, 3H, OCH ₃ ), 7.21 (d, 2H, J = 8.2 Hz, aromatic), 7.52 (d, 2H, J = 8.2 Hz, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.72 (CH ₃ ), 21.2 (CH ₃ ), 54.0 (CH ₃ ), 74.8 (C), 118.0 (C), 125. 5 (CH), 129.5 (CH), 133.5 (C), 139.9 (C), 167.6 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 300.1032 found 300.1018;
Elemental analysis: Calculated value of C ₁₄ H ₁₉ NO ₃ Si: C, 60.62, H, 6.90, N, 5.05. Found: C, 60.62, H, 6.74, N, 5.03;
Chiral HPLC analysis: column, CHIRALPAK AD-H; eluent, hexane: 2-propanol = 99: 1; flow rate 0.5 mL / min; column temperature, 40 ° C .; detection, UV254 nm; main component t _R , 6.4 Minute (97.8%); minor component t _R , 7.0 minutes (2.2%);
[Α] _D ²⁷ 27.08 ° (c 1.203, CHCl ₃ ), 95% ee.

(+)-Methyl 2-cyano-2- (3-chlorophenyl) -2-trimethylsilyloxyacetate (Compound No. 2h)
97% yield;
Colorless oil;
100 ° C./0.05 mmHg (valve / bulb);
IR (KBr—undiluted) 2958, 1769, 1474, 1426, 1256, 1196, 1155, 851, 769 cm ⁻¹ ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.29 (s, 9H, Si (CH ₃ ) ₃ ), 3.81 (s, 3H, OCH ₃ ), 7.33-7.40 (m, 2H, Aromatic), 7.54 (dt, 1H, J = 1.8, 7.3 Hz, aromatic), 7.63 (t, 1H, J = 1.8 Hz, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.66 (CH ₃ ), 54.3 (CH ₃ ), 74.2 (C), 117.5 (C), 123.7 (CH), 125.7 (CH), 130.0 (CH), 130.1 (CH), 134.9 (C), 138.3 (C), 167.1 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 320.0480, found 320.0479;
Elemental analysis: C ₁₃ H ₁₆ ClNO ₃ Si Calculated: C, 52.43, H, 5.42 , N, 4.70, Cl, 11.90. Found: C, 52.28, H, 5.26, N, 4.77, Cl, 11.97;
Chiral GC analysis: column, CHIRALDEX G-TA (0.25 mm × 30 m); carrier gas helium (100 kPa): column temperature, heated from 70 ° C. to 140 ° C. at a rate of 0.3 ° C./min; main component t _R 194.1 min (98.9%); minor component t _R , 196.0 min (1.1%); [α] _D ²⁷ 13.48 ° (c 1.031, CHCl ₃ ), 98% ee.

(+)-Methyl 2-cyano-2- (4-chlorophenyl) -2-trimethylsilyloxyacetate (Compound No. 2i)
98% yield;
Colorless oil;
103 ° C./0.07 mmHg (valve / bulb);
IR (KBr-undiluted) 2958, 1768, 1490, 1255, 1198, 1153, 1094, 872, 851 cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.28 (s, 9H, Si (CH ₃ ) ₃ ), 3.80 (s, 3H, OCH ₃ ), 7.37-7.40 (m, 2H, Aromatic), 7.57-7.61 (m, 2H, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.68 (CH ₃ ), 54.2 (CH ₃ ), 74.3 (C), 117.6 (C), 127.0 (CH), 129.0 (CH), 134.9 (C), 135.9 (C), 167.2 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 320.0486, found 320.0496;
Elemental analysis: Calculated value of C ₁₄ H ₁₉ NO ₃ Si: C, 52.43, H, 5.42, N, 4.70, Cl, 11.90. Found: C, 52.48, H, 5.29, N, 4.66, Cl, 11.93;
Chiral GC analysis: column, CHIRALDEX G-TA (0.25 mm × 30 m); carrier gas helium (100 kPa): column temperature, heated from 50 ° C. to 160 ° C. at a rate of 0.5 ° C./min; main component t _R 218.2 minutes (98.9%); minor component t _R , 220.6 minutes (1.1%);
^{_{[Α] D 25 22.19 ° (}} c 1.326, CHCl 3), 98% ee.

(+)-Methyl 2-cyano-2- (4-trifluoromethylphenyl) -2-trimethylsilyloxyacetate (Compound No. 2j)
92% yield;
Colorless oil;
101 ° C./0.23 mmHg (valve / bulb);
IR (KBr-undiluted) 2961, 1770, 1327, 1257, 1172, 1132, 1070, 873, 849 cm ⁻¹ ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.30 (s, 9H, Si (CH ₃ ) ₃ ), 3.81 (s, 3H, OCH ₃ ), 7.69 (d, 2H, J = 8.61 Hz, aromatic H) , 7.80 (d, 2H, J = 8.61 Hz, aromatic H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.59 (CH ₃ ), 54.3 (CH ₃ ), 74.4 (C), 117.6 (C), 123.6 (q, C, ¹ J _CF = 272.8 Hz), 125.8 (q, CH, ³ J _CF = 3.49 Hz), 126.1 (CH), 132.0 (q, C, ² J _CF = 32.4 Hz), 140.2 (C ), 167.0 (C)
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated value 354.0744, measured value 354.0754;
Elemental analysis: Calculated value of C ₁₄ H ₁₉ NO ₃ Si: C, 50.74, H, 4.87, N, 4.23. Actual value: C, 50.47, H, 4.79, N, 4.20;
Chiral GC analysis: column, CHIRALDEX G-TA (0.25 mm × 30 m); carrier gas helium (100 kPa): column temperature, heated from 50 ° C. to 170 ° C. at a rate of 3 ° C./min; main component t _R , 35 4 minutes (96.2%); minor component t _R , 35.7 minutes (3.8%);
[α] _D ²⁶ 12.71 ° (c 0.990, CHCl ₃ ), 92% ee.

(+)-Methyl 2-cyano-2- (4-methoxyenyl) -2-trimethylsilyloxyacetate (Compound No. 2k)
96% yield;
Colorless oil;
112 ° C./0.06 mmHg (valve / valve);
IR (KBr-undiluted) 2958, 2838, 1765, 1509, 1254, 872, 846 cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.24 (s, 9H, Si (CH ₃ ) ₃ ), 3.78 (s, 3H, OCH ₃ ), 3.82 (s, 3H, OCH ₃ ), 6.92 (m, 2H, aromatic), 7.55 (m, 2H, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.69 (CH ₃ ), 53.9 (CH ₃ ), 55.3 (CH ₃ ), 74.5 (C), 114.1 (CH), 118. 0 (C), 127.0 (CH), 128.3 (C), 160.6 (C), 167.6 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 316.0981, found 316.0991;
Elemental analysis: Calculated value of C ₁₄ H ₁₉ NO ₃ Si: C, 57.31, H, 6.53, N, 4.77. Found: C, 57.11, H, 6.41, N, 4.70;
Chiral HPLC analysis: column, CHIRALPAK AD-H; eluent, hexane: 2-propanol = 99: 1; flow rate 0.2 mL / min; column temperature, 40 ° C .; detection, UV254 nm; main component t _R , 24.1 Min (97.6%); minor component t _R , 26.1 min (2.4%); [α] _D ²⁶ 29.81 ° (c 1.270, CHCl ₃ ), 95% ee.

(+)-Methyl 2-cyano-2- (naphth-2-yl) -2-trimethylsilyloxyacetate (Compound No. 2l)
97% yield;
Colorless oil; 129 ° C./0.07 mmHg (bulb / bulb);
IR (KBr-undiluted) 3059, 2957, 2901, 1767, 1256, 1173, 1138, 874, 849 cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.29 (s, 9H, Si (CH ₃ ) ₃ ), 3.78 (s, 3H, OCH ₃ ), 7.52 to 7.56 (m, 2H, Aromatic), 7.67-7.70 (dd, 1H, J = 1.8, 8.6 Hz, aromatic), 7.83-7.93 (m, 3H, aromatic), 8.16 ( d, 1H, J = 1.8 Hz, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.79 (CH ₃ ), 54.1 (CH ₃ ), 75.1 (C), 118.0 (C), 122.4 (CH), 125.4 (CH), 126.9 (CH), 127.3 (CH), 127.7 (CH), 128.5 (CH), 128.9 (CH), 132.7 (C), 133, 6 ( C), 133.7 (C), 167.5 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 336.1032, found 336.1034;
Elemental analysis: Calculated value of C ₁₇ H ₁₉ NO ₃ Si: C, 65.15, H, 6.11, N, 4.47. Found: C, 65.30, H, 6.19, N, 4.25;
Chiral HPLC analysis: column, CHIRALPAK AD-H; eluent, hexane: 2-propanol = 99: 1; flow rate 0.5 mL / min; column temperature, 40 ° C .; detection, UV254 nm; main component t _R , 9.1 Minute (99.0%); minor component t _R , 10.4 minutes (1.0%);
[Α] _D ²⁴ 48.89 ° (c 0.995, CHCl ₃ ), 98% ee.

(+)-Methyl 2-cyano-2- (fur-3-yl) -2-trimethylsilyloxyacetate (Compound No. 2m)
94% yield;
Colorless oil; 113 ° C./0.50 mmHg (bulb / bulb);
IR (KBr-undiluted) 3153, 2959, 1771, 1255, 1168, 1146, 873, 849; ¹ H NMR (400 MHz, CDCl ₃ ): δ0.25 (s, 9H, Si (CH ₃ ) ₃ ), 1.55 (s, 3H), OCH ₃ ), 6.52 (dd, 1H, J = 0.91, 1.81 Hz, aromatic H), 7.42 (dd, 1H, J = 1.81, 1.81 Hz, aromatic H), 7.66 (dd , 1H, J = 0.91, 1.81 Hz, Aromatic H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ0.70 (CH ₃ ), 54.1 (CH ₃ ), 69.2 (C), 108.5 (CH), 117.4 (C), 123.6 (C), 141.1 (CH), 144.1 (CH), 166.9 (C); HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated value 276.0663, actual value 276.0669; chiral HPLC analysis: Column, CHIRALPAK AD-H; eluent, hexane: 2-propanol = 99: 1; flow rate 0.2 mL / min; column temperature, 40 ° C .; detection, UV254 nm; main component t _R , 16.7 min (95. 7%); minor component t _R , 15.0 minutes (4.3%);
[Α] _D ²⁷ 21.64 ° (c 0.975, CHCl ₃ ), 92% ee.

(+)-Methyl 2-cyano-2- (thien-2-yl) -2-trimethylsilyloxyacetate (Compound No. 2n)
99% yield;
Colorless oil;
87 ° C./0.45 mmHg (valve / valve);
IR (KBr-undiluted) 2959, 1770, 1436, 1255, 1134, 867, 849 cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.26 (s, 9H, Si (CH ₃ ) ₃ ), 3.86 (s, 3H, OCH ₃ ), 7.00 (dd, 1H, J = 3. 85, 5.21 Hz, aromatic), 7.33 (dd, 1 H, J = 1.14, 3.85 Hz, aromatic), 7.37 (dd, 1 H, J = 1.14, 5.21 Hz, Aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.56 (CH ₃ ), 54.3 (CH ₃ ), 71.9 (C), 117.3 (C), 126.7 (CH), 127.0 (CH), 127.8 (CH), 139.9 (C), 166.7 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 292.0440, found 292.0431;
Elemental analysis: C ₁₁ H ₁₅ NO ₃ SSi Calculated: C, 49.04, H, 5.61 , N, 5.20, S, 11.90. Found: C, 48.67, H, 5.38, N, 5.22, S, 11.74;
Chiral GC analysis: column, InertCap CHIRAMIX (0.25 mm × 30 m); carrier gas helium (100 kPa): column temperature, heated from 70 ° C. to 160 ° C. at a rate of 0.6 ° C./min; main component t _R , 141 2 minutes (95.8%);
[Α] _D ²⁷ 28.32 ° (c 1.020, CHCl ₃ ), 91% ee.

(−)-Methyl 2-cyano-3,3-dimethyl-2-trimethylsilyloxybutyrate (Compound No. 2o)
94% yield;
Colorless oil;
103 ° C./0.07 mmHg (valve / bulb);
IR (KBr-undiluted) 2962, 1762, 1255, 1149, 876, 846 cm ^-1 ;
¹ H NMR (400 MHz, CDCl ₃ ): δ 0.23 (s, 9H, Si (CH ₃ ) ₃ ), 1.07 (s, 9H, CH ₃ ), 3.84 (s, 3H, OCH ₃ );
¹³ C NMR (100 MHz, CDCl ₃ ): δ 0.29 (CH ₃ ), 24.7 (CH ₃ ), 40.2 (C), 53.1 (CH ₃ ), 80.1 (C), 118. 0 (C), 167.8 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated 266.1188, found 266.1198;
Chiral GC analysis: column, CP-Chirasil-Dex (0.32 mm × 25 m); carrier gas helium (72 kPa): column temperature, heated from 50 ° C. to 110 ° C. at a rate of 2.0 ° C./min; _R , 22.3 minutes (96.8%); minor component t _R , 22.5 minutes (3.2%);
^{_{[Α] D 23 -8.32 ° (}} c 1.019, CHCl 3), ee 94%.

(−)-Methyl 2-cyano-2-cyclohexyl-2-trimethylsilyloxyacetate (Compound No. 2p)
98% yield;
Colorless oil; 119 ° C / 0.2 mmHg (bulb / bulb);
IR (KBr-undiluted) 2935, 2857, 1766, 1255, 1168, 852;
¹ H NMR (400 MHz, CDCl ₃ ): δ0.23 (s, 9H, Si (CH ₃ ) ₃ ), 1.11-1.29 (m, 5H), 1.65-1.95 (m, 6H), 3.84 (s, 3H, OCH ₃ ); ¹³ C NMR (100 MHz, CDCl ₃ ): δ0.51 (CH ₃ ), 25.6 (CH ₂ ), 25.7 (CH ₂ ), 26.2 (CH ₂ ), 26.8 (CH ₂ ), 46.9 (CH ), 53.4 (CH ₃ ), 77.1 (C), 117.7 (C), 168.4 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated value 292.1339, actual value 292.1346;
Chiral HPLC analysis: column, CHIRALPAK IC; eluent, hexane: 2-propanol = 99: 1; flow rate 0.5 mL / min; column temperature, 40 ° C .; detection, UV 220 nm; main component t _R , 9.9 min ( 92.4%); minor component t _R , 9.3 minutes (7.6%);
[α] _D ²⁷ −1.58 ° (c 0.997, CHCl ₃ ), 85% ee.

(−)-Methyl 2-cyano-2- (cyclohexen-1-yl) -2-trimethylsilyloxyacetate (Compound No. 2q)
98% yield;
Colorless oil; 107 ° C / 0.1 mmHg (bulb / bulb);
IR (KBr—undiluted) 2937, 1765, 1254, 875, 850 cm ⁻¹ ;
¹ H NMR (400 MHz, CDCl ₃ ): δ0.26 (s, 9H, Si (CH ₃ ) ₃ ), 1.54-1.69 (m, 4H, CH ₂ ), 1.92−2.12 (m, 4H), 3.84 ( s, 3H, OCH ₃ ), 6.22-6.24 (m, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ0.70 (CH ₃ ), 21.6 (CH ₂ ), 22.2 (CH ₂ ), 23.1 ( CH ₂ ), 25.1 (CH ₂ ), 53.7 (CH ₃ ), 76.4 (C), 117.4 (C), 127.9 (CH), 133.0 (C), 167.5 (C);
HRMS (ESI ⁺ ), m / z (M + Na ⁺ ) calculated value 290.1183, actual value 290.1189;
Chiral HPLC analysis: column, CHIRALPAK IC; eluent, hexane: 2-propanol = 99: 1; flow rate 0.2 mL / min; column temperature, 40 ° C .; detection, UV 230 nm; main component t _R , 27.5 min ( 98.4%); minor component t _R , 26.0 minutes (1.6%);
[α] _D ²⁶ 31.07 ° (c 0.970, CHCl ₃ ); 97% ee.

Claims (5)

An optically active cyanohydrin compound represented by the general formula (1).
(In the general formula (1), R ₁ is a chain alkyl group which may have a branch, a cyclic alkyl group which may have a substituent, a chain alkenyl group which may have a branch, A cyclic alkenyl group which may have a substituent, an aryl group which may have a substituent, or a heterocyclic ring which may have a substituent, R ₂ represents a hydrogen atom, an alkali metal, a substituent R ₃ represents an alkyl group, an alkenyl group, an allyl group, or an aryl group, and represents a hydrocarbon group that may have a group or a silyl group that may have a substituent, and R ₁ and R ₃ may combine to form a lactone.) In the presence of a cyanation catalyst represented by the following general formula (2),
(In the general formula (2), R _{4 to} R ₇ may be the same or different, and each may be a hydrocarbon group which may have a substituent, and R ₄ and R ₅ and / or R _6. And R ₇ may form an optionally substituted carbon chain ring; R _{8 to} R ₁₁ may be the same or different, and each may have a hydrogen atom or a substituent. A good hydrocarbon group, R ₈ and R ₉ and / or R ₁₀ and R ₁₁ may form an optionally substituted carbon chain ring; R ₁₂ and R ₁₃ may be the same or each Hydrocarbon groups which may be different and each may have a hydrogen atom or a substituent; W, X and Y may be the same or different and each may have a substituent Where X and / or Y may not be present; M represents a metal or metal ion; Each ligand may be arranged how)
The following general formula (3)
(In the general formula (3), R ₁ is a chain alkyl group which may have a branch, a cyclic alkyl group which may have a substituent, a chain alkenyl group which may have a branch, A cyclic alkenyl group which may have a substituent, an aryl group which may have a substituent, or a heterocyclic ring which may have a substituent, R ₃ represents an alkyl group, an alkenyl group, an allyl. A group or an aryl group.)
A ketoester compound represented by the following general formula (4):
(In General Formula (4), R ₂ represents a hydrogen atom, an alkali metal, a hydrocarbon group which may have a substituent, or a silyl group which may have a substituent.)
The method for producing an optically active cyanohydrin compound according to claim 1, comprising a step of reacting with a cyanide compound represented by the formula: and a step of reacting a metal compound salt added to the reaction product obtained in the step. . In the presence of a cyanation catalyst obtained by reacting a cyanation catalyst represented by the following general formula (2) with a salt of a metal compound,
(In the general formula (2), R _{4 to} R ₇ may be the same or different, and each may be a hydrocarbon group which may have a substituent, and R ₄ and R ₅ and / or R _6. And R ₇ may form an optionally substituted carbon chain ring; R _{8 to} R ₁₁ may be the same or different, and each may have a hydrogen atom or a substituent. A good hydrocarbon group, R ₈ and R ₉ and / or R ₁₀ and R ₁₁ may form an optionally substituted carbon chain ring; R ₁₂ and R ₁₃ may be the same or each Hydrocarbon groups which may be different and each may have a hydrogen atom or a substituent; W, X and Y may be the same or different and each may have a substituent Where X and / or Y may not be present; M represents a metal or metal ion; Each ligand may be arranged how)
The following general formula (3)
(In the general formula (3), R ₁ is a chain alkyl group which may have a branch, a cyclic alkyl group which may have a substituent, a chain alkenyl group which may have a branch, A cyclic alkenyl group which may have a substituent, an aryl group which may have a substituent, or a heterocyclic ring which may have a substituent, R ₃ represents an alkyl group, an alkenyl group, an allyl. A group or an aryl group.)
A ketoester compound represented by the following general formula (4):
(In General Formula (4), R ₂ represents a hydrogen atom, an alkali metal, a hydrocarbon group which may have a substituent, or a silyl group which may have a substituent.)
The manufacturing method of the optically active cyanohydrin compound of Claim 1 including the process with which the cyanide compound represented by these is made to react.   The method for producing an optically active cyanohydrin compound according to claim 2 or 3, wherein M in the general formula (2) is divalent ruthenium.   The method for producing an optically active cyanohydrin compound according to any one of claims 2 to 4, wherein W in the general formula (2) is a 1,1'-binaphthyl group or a 1,1'-biphenyl group.