JP4943185B2 - Process for producing optically active sulfonylimine compound - Google Patents

Description

  The present invention comprises reacting an enesulfonamide and a compound having an aldehyde group in an organic solvent in the presence of a catalyst containing a copper compound and a diimine containing an asymmetric carbon atom, The present invention relates to a method for producing a sulfonylimine compound, and a hydrolyzate and a reduced product thereof.

In the field of fine chemicals such as pharmaceuticals, agricultural chemicals, fragrances, and functional polymers, it has been desired to provide substances with higher purity from the viewpoint of the effectiveness and safety of chemical substances. In particular, for substances having an asymmetric carbon atom in the molecule, it has been desired to provide optically higher-purity substances, and development of methods for producing stereoselective or enantioselective chemical substances is desired. It is rare. Such a production method is generally called an asymmetric synthesis method, and the asymmetric hydrogenation reaction has already been industrialized.
Catalytic asymmetric aldol reaction has been actively studied as an enantioselective production method for compounds having carbonyl groups and hydroxyl groups as a method for synthesizing important compounds in the fine chemical field. The side reaction was likely to occur, and the target product could not be obtained in a sufficient yield. In particular, when an aldehyde is used as a nucleophile, it is well known that it involves problems such as self-condensation and product re-reaction. In recent years, catalytic asymmetric cross-aldol reaction using aldehyde directly or aldehyde-derived silicon and enolate has been reported and attracted attention (see Non-Patent Documents 1 to 3).
In such a situation, the present inventors have reported a catalytic asymmetric nucleophilic addition reaction of ketone-derived encarbamate or enamide to imine, aldehyde, and ketone using a chiral copper catalyst (Patent Document 1). And non-patent documents 4 to 7).

However, simple enamines have been used in previous reports, and improvements to enamines have been sought. As one of the improvements, a nucleophilic addition reaction using a chiral azaenolate has been reported. Azaenolate has high nucleophilicity and is useful, and in particular, an asymmetric nucleophilic addition reaction using azaenolate has been considered useful because an optically active nitrogen-containing compound can be obtained.
On the other hand, in the field of the chemical industry, reduction of environmental load is an important issue, and in particular, attempts to synthesize asymmetric points from a catalytic amount of asymmetric sources are being actively studied. The conventional asymmetric nucleophilic addition reaction using chiral azaenolate is excellent in selectivity, but requires an equivalent amount of the asymmetric source, and often does not recover the asymmetric source after the reaction. Catalytic asymmetric addition reaction using azaenolate as a nucleophile has been studied, but only a very limited example has been reported.
In recent years, the present inventors have reacted enamides and encarbamates with various electrophiles such as ethyl glyoxylate, acylimine, and azodicarboxylate in the presence of a chiral Lewis acid catalyst to produce adducts in high yield and high yield. Finding to give selectively.

WO 2005/070864 Cordoba, A. and others J. Org. Chem. 2002, 67, 301. Chowdari, R. et al. Tetrahedron Lett. 2002, 43, 9951. Denmark, S. E. and others Angew. Chem., Int. Ed. 2001, 40, 4759. J.S. Fossey et al., Org. Biomol. Chem., 2005, 3, 2910-2913 R. Matasubara et al., Tetrahedron, 60, 2004, 9769-9784 R. Matasubara et al., Angew. Chem. Int. Ed., 2004, 43, 1679-1681 R. Matasubara et al., Angew. Chem. Int. Ed., 2004, 43, 3258-3260

  The present invention is a general formula (3), which is a raw material for producing pharmaceuticals, agricultural chemicals, fragrances, functional polymers and the like and a raw material for producing optically active amino alcohols and keto alcohols useful as synthetic intermediates. It aims at providing the method of manufacturing the represented sulfonyl imine compound by catalytic asymmetric nucleophilic addition reaction. More specifically, the present invention provides a stereoselection in a simple and high yield by an aldol addition-type catalytic asymmetric nucleophilic addition reaction using a carbonyl compound and an enamine derivative in the presence of a copper compound and an optically active diimine. It is an object of the present invention to provide a typical sulfonylimine compound and a method for producing a hydrolyzate and a reduced product thereof.

  In general, in an aldol addition reaction type nucleophilic addition reaction using a carbonyl compound and enamine or a derivative thereof, an adduct formed by the aldol addition reaction is hydrolyzed to produce an aldol derivative. Since both the starting carbonyl compound and enamine are carbonyl derivatives, side reactions such as self-condensation and oligomerization are likely to occur, and it may be difficult to isolate the product. In particular, when the enamine used is derived from an aldehyde, the product is complicated and it is difficult to obtain a sufficient yield. The present inventors further studied and found an aldol addition reaction type nucleophilic addition reaction using a new type of enamine derivative.

  That is, the present invention provides an enesulfonamide represented by the general formula (1) and a compound having an aldehyde group in the presence of a catalyst comprising a copper compound and a diimine containing an asymmetric carbon atom. The present invention relates to a method for producing a sulfonylimine compound represented by the general formula (3) and a hydrolyzate and a reduced product thereof by reacting them. The method of the present invention is stereoselective, and the present invention relates to an optically active sulfonylimine compound, and a method for efficiently producing a hydrolyzate and a reduced product thereof.

The present invention will be described more specifically as follows.
(1) The following general formula (1)

(In the formula, R ¹ and R ² each independently represent a hydrogen atom or an alkyl group which may have a substituent, and R ³ has an alkyl group or a substituent which may have a substituent. R ⁴ represents an aryl group which may have a substituent, and R ² and R ³ together with adjacent carbon atoms have 5 to 15 carbon atoms. A ring may be formed.)
An enesulfonamide represented by the following general formula (2):

(In the formula, R ⁵ represents a —R ^a group, a —C (═O) —R ^a group, or a —COO—R ^a group, and R ^a represents a hydrocarbon group which may have ^a substituent. .)
In the presence of a catalyst comprising a copper compound and a diimine containing an asymmetric carbon atom, and the following general formula (3):

(In the formula, R ¹ and R ² each independently represent a hydrogen atom or an alkyl group which may have a substituent , and R ³ has an alkyl group or a substituent which may have a substituent. represents an aryl group which may be, R ⁴ represents an aryl group which may have a substituent, and the carbon of 5 to 15 carbon atoms together with the carbon atoms to which R ² and R ³ are adjacent, together A ring may be formed, and R ⁵ represents a —R ^a group, a —C (═O) —R ^a group, or a —COO—R ^a group, and R ^a may be a carbon atom that may have ^a substituent. Represents a hydrogen group . )
A process for producing a sulfonylimine compound represented by the formula:
(2) R ⁵ in the general formula (2) is a —C (═O) —R ^a group or a —COO—R ^a group (wherein R ^a represents ^a hydrocarbon group which may have ^a substituent). The method according to (1), wherein
(3) The diimine containing an asymmetric carbon atom is an optically active substance, and the sulfonylimine compound represented by the general formula (3) to be generated contains an excess of at least one optically active substance. The method according to 2).
(4) The method according to any one of (1) to (3), wherein the sulfonylimine compound represented by the general formula (3) is an optically active substance.
(5) The method according to any one of (1) to (4), wherein the diimine containing an asymmetric carbon atom is a compound having an ethylenediamine structure.
(6) A diimine containing an asymmetric carbon atom is represented by the following general formula (4)

(In the formula, Ar ¹ and Ar ² each independently represent an aryl group which may have a substituent, and R ⁶ and R ⁷ each independently represent an alkyl group.)
The method in any one of said (1)-(5) which is an ethylenediamine derivative represented by these.
(7) The method according to any one of (1) to (6), wherein the copper compound is copper perchlorate.
(8) In the general formula (1), R ¹ and R ² each independently represent a hydrogen atom or a linear or branched alkyl group having 1 to 30 carbon atoms which may have a substituent, R ³ is a monocyclic or polycyclic group having 1 to 30 carbon atoms which may have a linear or branched alkyl group having 1 to 30 carbon atoms, or 6 to 36 carbon atoms which may have a substituent. Or a condensed cyclic carbocyclic aromatic group (aryl group), and R ⁴ may be a monocyclic, polycyclic or condensed cyclic group having 6 to 36 carbon atoms which may have a substituent. The method according to any one of (1) to (7) above, which represents a carbocyclic aromatic group (aryl group).
(9) In the general formula (1), the carbocyclic ring having 5 to 15 carbon atoms together with the adjacent carbon atom in which R ² and R ³ are combined is a cycloalkene ring having 5 to 15 carbon atoms (1 ) To (8).
(10) The substituent in the alkyl group or aryl group is derived from halogen, a linear or branched alkyl group having 1 to 20 carbon atoms, or a linear or branched alkyl group having 1 to 20 carbon atoms. The method according to any one of (1) to (9) above, which is an alkoxy group.
(11) A method for producing a corresponding 3-ketoalcohol derivative in which the imino group is converted to a keto group (= O) by hydrolyzing the sulfonylimine compound represented by the general formula (3).
(12) The method according to (11), wherein the hydrolysis is performed in the presence of an acid.
(13) The corresponding sulfonylimine compound represented by the general formula (3) is reduced to produce a corresponding 3-aminoalcohol derivative in which the imino group is an amide group (—N—SO ₂ —). Method.
(14) The method according to (13), wherein the reduction is reduction with a hydride.

Next, aspects of the present invention will be described in more detail.
First, an aldol addition type nucleophilic addition reaction of an enesulfonamide represented by the general formula (1) with an aldehyde group of a compound having an aldehyde group according to the present invention will be described.
The “compound having an aldehyde group” in the present invention has an aldehyde group (—CHO group) and has a carbon atom bonded to one end of the aldehyde group, and causes a side reaction under reaction conditions. There is no particular limitation as long as it does not have a functional group. And since reaction with respect to the said aldehyde group (-CHO group) is a nucleophilic reaction, it has an electron withdrawing functional group, and the electron in the carbon atom of the said aldehyde group (-CHO group) becomes a deficient system. Are preferred.
If the “compound having an aldehyde group” in the present invention is more specifically shown, the following general formula (2)

(In the formula, R ¹ represents a —R ^a group, a —C (═O) —R ^a group, or a —COO—R ^a group, and R ^a represents a hydrocarbon group that may have ^a substituent. .)
The compound represented by these is mentioned.
As the hydrocarbon group of the group R ^a in the general formula (2), ^a linear or branched alkyl group having 1 to 20 carbon atoms, preferably 1 to 15 carbon atoms and 1 to 10 carbon atoms; A linear or branched alkenyl group having 2 to 20, preferably 2 to 15 carbon atoms and 2 to 10 carbon atoms; a straight chain or branched alkenyl group having 2 to 20 carbon atoms, preferably 2 to 15 carbon atoms, and a straight chain having 2 to 10 carbon atoms. A chain or branched alkynyl group; a saturated or unsaturated monocyclic, polycyclic or condensed cyclic alicyclic hydrocarbon group having 3 to 15 carbon atoms, preferably 3 to 10 carbon atoms; 6-36, preferably 6-18, monocyclic, polycyclic or condensed cyclic carbocyclic aromatic group having 6-12 carbon atoms; 6-36 carbon atoms, preferably 6-6 carbon atoms 18. The number of carbon atoms described above in a monocyclic, polycyclic or condensed cyclic carbocyclic aromatic group (aryl group) having 6 to 12 carbon atoms Examples thereof include an aralkyl group (carbocyclic araliphatic group) having 7 to 40 carbon atoms, preferably 7 to 20 carbon atoms and 7 to 15 carbon atoms, to which an alkyl group having 1 to 20 is bonded. Examples of these hydrocarbon groups include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, Octyl group, vinyl group, 1-methyl-vinyl group, 2-methyl-vinyl group, n-2-propenyl group, 1,2-dimethyl-vinyl group, 1-methyl-propenyl group, 2-methyl-propenyl group, n-1-butenyl group, n-2-butenyl group, n-3-butenyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group, cyclooctyl group, bicyclo [1.1.0] butyl group, tricyclo [2. 2.1.0] heptyl group, bicyclo [3.2.1] octyl group, bicyclo [2.2.2. ] Octyl group, adamantyl group (tricyclo [3.3.1.1] decanyl group), bicyclo [4.3.2] undecanyl group, tricyclo [5.3.1.1] dodecanyl group, phenyl group, naphthyl group , Biphenyl group, phenanthryl group, anthryl group, benzyl group, phenethyl group, α-naphthyl-methyl group and the like. The substituents in these hydrocarbon groups include halogen atoms such as chlorine and bromine atoms; alkoxy groups derived from the aforementioned alkyl groups; alkoxycarbonyl groups derived from the aforementioned alkyl groups; An alkylcarbonyloxy group derived from: a cycloalkoxy group derived from the above cycloalkyl group; a cycloalkoxycarbonyl group derived from the above cycloalkyl group; a cycloalkylcarbonyloxy group derived from the above cycloalkyl group An aryloxy group derived from the carbocyclic aromatic group; an aryloxycarbonyl group derived from the carbocyclic aromatic group; an arylcarbonyloxy group derived from the carbocyclic aromatic group; Derived from the aralkyl groups described above An aralkyloxycarbonyl group; an aralkyloxycarbonyl group derived from the aralkyl group; an aralkylcarbonyloxy group derived from the aralkyl group; a cyano group; a nitro group; A cycloalkyl group or the like can also be used as a substituent.

Among the compounds having an aldehyde group represented by the general formula (2), as a more preferable compound, the group R ¹ in the general formula (1) is a —C (═O) —R ^a group or a —COO—R ^a group. There are some cases. In the method of the present invention, the compound having an aldehyde group represented by the general formula (2) is more preferably the following general formula (5).

(In the formula, R ⁸ represents a hydrocarbon group which may have a substituent or a hydrocarbon oxy group which may have a substituent.)
The compound represented by these is mentioned. Examples of the hydrocarbon group which may have a substituent in the general formula (5) include the same groups as those described as the group R ^a described above. Preferred R ⁸ is a linear or branched alkyl group having 1 to 20 carbon atoms, preferably 1 to 15 carbon atoms and 1 to 10 carbon atoms; an oxygen atom in the above alkyl group having 1 to 20 carbon atoms; An alkoxy group having 6 to 36 carbon atoms, preferably 6 to 18 carbon atoms, a monocyclic, polycyclic or condensed cyclic aryl group having 6 to 12 carbon atoms, an oxygen atom in the above-described aryl group A bonded aryloxy group; a monocyclic, polycyclic or condensed cyclic carbocyclic aromatic group (aryl group) having 6 to 36 carbon atoms, preferably 6 to 18 carbon atoms and 6 to 12 carbon atoms. An aralkyl group having 7 to 40 carbon atoms, preferably 7 to 20 carbon atoms and 7 to 15 carbon atoms, to which the alkyl group having 1 to 20 carbon atoms is bonded; an aralkyloxy having an oxygen atom bonded to the aralkyl group described above Group and the like. Examples of the substituent of these groups include the substituent groups described above.
Specific examples of preferable “compound having an aldehyde group” in the method of the present invention include glyoxylic acid esters such as glyoxylic acid ethyl ester and glyoxal such as phenylglyoxal.

The alkyl group in the enesulfonamide represented by the general formula (1) in the method of the present invention is a linear or branched group having 1 to 30 carbon atoms, preferably 1 to 15 carbon atoms and 1 to 10 carbon atoms. Of the alkyl group. The aryl group is a monocyclic, polycyclic or condensed cyclic carbocyclic aromatic group (aryl group) having 6 to 36 carbon atoms, preferably 6 to 18 carbon atoms and 6 to 12 carbon atoms. Is mentioned. Examples of such an aryl group include a phenyl group, a naphthyl group, a biphenyl group, a phenanthryl group, and an anthryl group. These alkyl groups and aryl groups can have various substituents as long as they do not adversely affect the reaction. As such a substituent, a halogen atom such as a chlorine atom or a bromine atom, a straight chain having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms such as a methoxy group or an ethoxy group. And an alkoxy group derived from a linear or branched alkyl group. Moreover, as a substituent of an aryl group, the C1-C30 alkyl group mentioned above may be sufficient.
Preferred enesulfonamides of the present invention include N- (benzenesulfonyl)-(E) -1-phenyl-1-propenyl-amine, N- (benzenesulfonyl)-(Z) -1-phenyl-1-propenyl- Amine, N- (p-methoxy-benzenesulfonyl)-(E) -1-phenyl-1-propenyl-amine, N- (p-methoxy-benzenesulfonyl)-(Z) -1-phenyl-1-propenyl- Amine, N- (p-methyl-benzenesulfonyl)-(E) -1-phenyl-1-propenyl-amine, N- (p-methyl-benzenesulfonyl)-(Z) -1-phenyl-1-propenyl- Amine, N- (p-chloro-benzenesulfonyl)-(E) -1-phenyl-1-propenyl-amine, N- (p-chloro-benzenesulfonyl)- Z) -1-phenyl-1-propenyl-amine, N- (p-methoxy-benzenesulfonyl)-(E) -1- (p-methoxy-phenyl) -1-propenyl-amine, N- (p-methoxy -Benzenesulfonyl)-(Z) -1- (p-methoxy-phenyl) -1-propenyl-amine, N- (p-methoxy-benzenesulfonyl)-(E) -1- (p-chloro-phenyl)- 1-propenyl-amine, N- (p-methoxy-benzenesulfonyl)-(Z) -1- (p-chloro-phenyl) -1-propenyl-amine, N- (p-methoxy-benzenesulfonyl)-(E ) -1-phenyl-1-butenyl-amine, N- (p-methoxy-benzenesulfonyl)-(Z) -1-phenyl-1-butenyl-amine, N- (p-methoxy-benzene) Ruhoniru) - (E) -2- pentenyl - amine, N-(p-methoxy - benzenesulfonyl) - (Z) -2- penten-1-yl - amine and the like.

  The use ratio of the compound having an aldehyde group and the enesulfonamide represented by the general formula (1) in the method of the present invention is basically 1: 1, but the reactivity and price of the raw material compound, etc. Can be determined as appropriate. The molar ratio of the two can be selected within a wide range of about 0.1 to 10.

The enesulfonamide represented by the general formula (1) is added to the aldehyde group of the compound having an aldehyde group of the present invention as an aldol addition type nucleophilic addition reaction under the reaction conditions of a normal aldol addition reaction. However, a method for obtaining an enantioselective product in the presence of a chiral catalyst as a catalyst is preferred. As such a method, various kinds of chiral catalysts can be used, but the use of the chiral catalyst previously reported by the present inventors (see WO 2005/070864) is preferred. For example, the catalyst may be a chiral copper catalyst or a chiral nickel catalyst. The chirality in these catalysts can be generated by the organic compound used as the ligand.
Preferable examples of the ligand having such a chirality include diimine compounds. A compound having an alkylene diamine structure, more specifically an ethylene diamine structure is more preferable. A preferred example of a chiral ligand that is an asymmetric carbon atom-containing ligand is an ethylenediamine compound represented by the above general formula (4). Examples of the alkyl group in the groups R ⁶ and R ⁷ in the general formula (4) include linear or branched alkyl groups having 1 to 20 carbon atoms, preferably 1 to 15 carbon atoms and 1 to 10 carbon atoms. Examples thereof include an n-butyl group and a t-butyl group. The aryl group in the groups Ar ¹ and Ar ² is a monocyclic, polycyclic or condensed cyclic aryl group having 6 to 36 carbon atoms, preferably 6 to 18 carbon atoms, and 6 to 12 carbon atoms. Can be mentioned. Examples of such an aryl group include a phenyl group, a naphthyl group, a biphenyl group, a phenanthryl group, and an anthryl group. Preferred aryl groups include phenyl and naphthyl groups. Examples of the substituent for the alkyl group or aryl include substituents which have been described in the group R ^a as described above. As a preferable substituent in the aryl group, a halogen atom such as a chlorine atom or a bromine atom; a straight chain having 1 to 30 carbon atoms such as a methyl group or an ethyl group, preferably 1 to 15 carbon atoms, or 1 to 10 carbon atoms; A branched alkyl group; derived from a linear or branched alkyl group having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, such as a methoxy group or an ethoxy group; An alkoxy group etc. are mentioned. One or two or more of these substituents may be used.
Among these, more preferred diimines containing an asymmetric carbon atom include the following.

(In formula, R shows a C1-C20 linear or branched alkyl group each independently, or a C6-C36 aryl group which may have a substituent.)
The diamine diamine derivative or cyclohexyl diamine derivative represented by these is mentioned. The Ph group or aryl group in the above formula may have one or more substituents, and examples of such substituents include a methyl group, an ethyl group, an i-propyl group, and a t-butyl group. A linear or branched alkyl group having 1 to 10 carbon atoms such as a group; a linear or branched alkoxy group having 1 to 10 carbon atoms such as a methoxy group or an ethoxy group; a chlorine atom, a fluorine atom, And halogen atoms such as bromine atom. More preferred Ph groups and aryl groups include unsubstituted phenyl groups, halogen-substituted phenyl groups such as p-bromophenyl groups, and alkyl-substituted phenyl groups such as 3,5-xylyl groups. Particularly preferable examples of the aryl group include a p-bromophenyl group, and examples of the Ph group include a phenyl group or a 3,5-xylyl group.

The copper compound may be selected from a variety of monovalent or divalent compounds such as copper salts, complex salts, and organometallic compounds. Among them, a salt with an organic acid or an inorganic acid, or a salt thereof Complexes and organic complexes are preferred. More preferably, a salt with a strong acid, for example, a salt of perfluoroalkylsulfonic acid, perchloric acid, sulfuric acid or the like, a complex or an organic complex thereof can be used. Examples of such a copper compound include Cu (OTf) ₂ , CuOTf, CuClO ₄ .4CH ₃ CN, Cu (ClO ₄ ) ₂ .6H ₂ O, Ni (OTf) ₂ , NiX ₂ + AgOTf (X is a halogen atom) And the like. Preferred copper compounds include copper perchlorate and its solvate CuClO ₄ · 4CH ₃ CN.
The copper compound in the method of the present invention may be prepared by previously mixing a copper compound as described above and a diimine containing a chiral asymmetric carbon atom to prepare a complex, which may be used as a catalyst. Alternatively, a copper compound and a compound containing an asymmetric carbon atom may be mixed and used in the reaction system. About the use ratio as a catalyst, it is 0.1-50 mol% normally as a complex of a copper compound and a chiral organic molecule with respect to an aldehyde compound, Preferably it is a ratio of about 0.5-20 mol%. can do.

The method of nucleophilic addition reaction of enesulfonamide represented by the general formula (1) to the aldehyde group of the compound having an aldehyde group of the present invention is an aldol addition type halophilic hydrocarbon such as methylene chloride, acetonitrile or the like. It is preferably carried out in the presence of an organic solvent such as nitriles and ethers such as THF. The reaction temperature can be appropriately selected within the range of preferably −20 ° C. to the boiling point of the solvent and about −20 ° C. to 40 ° C. The atmosphere can be air or an inert atmosphere.
By using the catalyst of the present invention as described above, the addition of enesulfonamide represented by the general formula (1) is stereoselectively generated, and the hydroxyl group generated at the position of the aldehyde group of the compound having an aldehyde group Either (R) or (S) is preferentially generated. In this specification, the excess of either the (R) isomer or the (S) isomer at this position is expressed as an enantiomeric excess (ee) (%). This enantiomeric excess is ((R) − (S)) / ((R) + (S)) × 100 or ((S) − (R)) / ((R) + (S)) × 100 Is calculated as
In the method of aldol addition type nucleophilic addition reaction of an enesulfonamide represented by the general formula (1) to an aldehyde group of a compound having an aldehyde group, an iminoalcohol is usually produced and hydrolyzed. An optically active aldol derivative (3-carbonyl alcohol derivative) can be obtained, and an optically active 3-amino alcohol can be produced by reducing this. These methods can be carried out as they are without isolating the sulfonylimine compound represented by the general formula (3) produced in the method of the present invention.
By hydrolyzing the sulfonylimine compound represented by the general formula (3), the corresponding 3-keto in which the imino group (= N) moiety in the general formula (3) is converted to a keto group (= O) Alcohol derivatives can be produced. As the acid used at this time, inorganic acids such as hydrochloric acid and hydrobromic acid can be used.
Further, the sulfonylimine compound represented by the general formula (3) is reduced so that the imino group (= N—SO ₂ —) moiety in the general formula (3) is an amide group (—N—SO ₂ —). The corresponding 3-amide-alcohol derivative can be prepared and further hydrolyzed to the corresponding 3-aminoalcohol derivative. As a reducing agent for reduction at this time, a hydride such as a borohydride compound, an aluminum hydride compound, or a salt thereof can be used. Specific examples of these will be described in Examples described later.

  The present invention is an optical material used as a raw material for optically active 1,3-amino alcohol derivatives and 1,3-carbonyl alcohol derivatives useful as raw materials and synthetic intermediates for the production of pharmaceuticals, agricultural chemicals, fragrances, functional polymers and the like. The present invention provides an efficient process for producing an active sulfonylimine derivative with high yield, high optical yield, and the ability to reuse a catalyst. In addition, the method of the present invention provides a method for the nucleophilic addition reaction of an enantioselective and diastereoselective glyoxylate to an aldehyde group, and a method for producing an optically active α-hydroxy acid ester and the like using the method. Is.

EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited at all by these Examples.
^{For 1} H-NMR and ¹³ C-NMR, JEOL JNM-ECX400, JNM-ECX500, or JNM-ECX600 is used, CDCl ₃ is used as a solvent (indicated separately when other solvents are used), and tetramethylsilane (δ = 0, ¹ H-NMR) or CDCl ₃ (δ = 77.0, ¹³ C-NMR) was used as an internal standard substance. JASCO FT / IR-610 was used for IR spectrum measurement and JASCO P-1010 was used for optical rotation measurement. For the measurement of HPLC, SHIMADZU LC-10AT, SHIMADZU SPD-10A and SHIMADZU C-R6A C were used. SHIMADZU GC-17A or SHIMADZU GCMS-QP5050A was used for mass spectrometry, and YAZAWA BY-1 was used for measuring the melting point. Silica gel 60 (Merck) was used for column chromatography, and Wakogel B-5F was used for preparative thin-layer chromatography. All the reactions were carried out under an argon atmosphere, and the solvent used was distilled according to a conventional method. Ethyl glyoxylate was distilled immediately before use.

Production of Ensulfonamide Represented by General Formula (1) Ensulfonamide is obtained by the method of Kato et al. (Kato, S .; Igami, S. JP 63250303 A2 (JP-A 63-250303) 1988-10-18 (Chem. Abstr. 111: 96854 1988)) Synthesized by the method described in the literature.
The physical property values of enesulfonamides produced by these methods are shown below. The numbers in parentheses after the compound name are the numbers of the compounds used in the following description.
Example 1-1
N- (benzenesulfonyl)-(E) -1-phenyl-1-propenyl-amine (E-4a).

Mp. 107-108 ° C;
¹ H NMR (CDCl ₃ ) δ:
1.60 (d, 3H, J = 7.3 Hz), 5.68 (q, 1H, J = 7.2 Hz), 6.03 (s, 1H),
6.95-7.10 (m, 2H), 7.20-7.30 (m, 3H), 7.45-7.63 (m, 3H),
7.82 (d, 2H, J = 7.8 Hz);
¹³ C NMR (CDCl ₃ ) δ:
13.9, 115.7, 127.4, 128.3, 128.3, 128.8, 128.9, 132.8, 133.8,
135.4, 139.7;
IR (neat) 3347, 3255, 2978, 1685, 1596, 1447, 1332, 1219, 1159,
1090, 951, 754, 688, 592, 536 cm ⁻¹ ;
HRMS (FAB); [M + H] ⁺ as calculated 274.9022.
Actual value 274.0911.
Example 1-2
N- (benzenesulfonyl)-(Z) -1-phenyl-1-propenyl-amine (Z-4a).

Mp. 104-104.5 ° C;
¹ H-NMR (CDCl ₃ ); δ:
1.47 (d, 3H, J = 6.8 Hz), 5.68 (q, 1H, J = 7.0 Hz), 6.18 (s, 1H),
7.20-7.27 (m, 3H), 7.30-7.37 (m, 2H), 7.38-7.45 (m, 2H),
7.50-7.55 (m, 1H);
¹³ C-NMR (CDCl ₃ ) δ:
13.0, 121.4, 126.8, 127.4, 128.1, 128.2, 128.9, 132.9,
135.1, 137.8, 139.8;
IR (neat) 3258, 3082, 3062, 3020, 2919, 1644, 1585, 1491, 1480,
1446, 1402, 1326, 1268, 1165, 1091, 1043, 1025, 997,
970, 904, 844, 787, 748, 727, 696, 685, 645, 620, 571,
532, 440 cm ⁻¹ ;
HRMS (FAB); [M + H] ⁺ as calculated 274.902.
Actual value 274.903.
Example 1-3
N- (p-methoxy-benzenesulfonyl)-(E) -1-phenyl-1-propenyl-amine (E-4b).

Mp. 52-54 ° C;
¹ H-NMR (CDCl ₃ ); δ:
1.59 (d, 3H, J = 7.3 Hz), 3.87 (s, 3H), 5.65 (q, 1H, J = 7.2 Hz),
5.95-6.02 (brs, 1H), 6.94 (d, 2H, J = 8.7 Hz), 7.00-7.07 (m, 2H),
7.22-7.27 (m, 3H), 7.70-7.78 (m, 2H);
¹³ C-NMR (CDCl ₃ ) δ:
13.9, 55.6, 114.0, 115.0, 128.3, 128.8, 129.6, 131.3, 134.0,
135.6, 163.0;
IR (neat) 3647, 3266, 3057, 2942, 2840, 1595, 1578, 1497, 1434,
1415, 1378, 1357, 1312, 1260, 1224, 1180, 1157, 1091,
1025, 960, 877, 834, 802, 781, 767, 700, 628, 577,
553 cm ⁻¹ ;
HRMS (FAB); Calculated as [M + H] ⁺ 304.1007.
Actual value 304.0996.
Example 1-4
N- (p-methoxy-benzenesulfonyl)-(Z) -1-phenyl-1-propenyl-amine (Z-4b).

Mp. 142.5-143.5 ° C;
¹ H-NMR (CDCl ₃ ); δ:
1.49 (d, 3H, J = 6.9 Hz), 3.84 (s, 3H), 5.64 (q, 1H, J = 7.1 Hz),
6.12 (s, 1H), 6.85-6.88 (m, 2H), 7.22-7.26 (m, 3H),
7.34-7.37 (m, 2H), 7.61-7.64 (m, 2H);
¹³ C-NMR (CDCl ₃ ) δ:
12.9, 55.6, 113.9, 120.7, 126.7, 127.9, 128.0, 129.4, 131.4,
135.3, 137.7, 163.0;
IR (neat) 3255, 1643, 1595, 1576, 1496, 1457, 1442, 1395, 1326,
1263, 1181, 1159, 1112, 1094, 1041, 1024, 968, 904, 833,
802, 785, 748, 695, 645, 612, 558, 539, 504, 448 cm ^-1 ;
HRMS (FAB); Calculated as [M + H] ⁺ 304.1007.
Actual value 304.0995.
Since this crystal was suitable for the measurement of X-ray diffraction, it was recrystallized from AcOEt / hexane and analyzed. This data can be obtained free of charge as CCDC-629330 by accessing www.ccdc.cam.ac.uk/conts/retrieving.htmlam.ac.uk/conts/retrieving.html.
Example 1-5
N- (p-methyl-benzenesulfonyl)-(Z) -1-phenyl-1-propenyl-amine (Z-4c).

Mp. 132-134 ° C;
¹ H-NMR (CDCl ₃ ); δ:
1.47 (d, 3H, J = 6.9 Hz), 2.41 (s, 3H), 5.66 (q, 1H, J = 7.2 Hz),
6.10 (s, 1H), 7.20-7.27 (m, 5H), 7.34-7.38 (m, 2H),
7.58-7.63 (m, 2H);
¹³ C-NMR (CDCl ₃ ) δ:
12.9, 21.5, 120.8, 126.7, 127.3, 127.9, 128.0, 129.4, 135.2,
136.7, 137.7, 143.6;
IR (neat) 3263, 3032, 1646, 1596, 1492, 1444, 1395, 1326, 1164,
1091, 1040, 1025, 899, 834, 813, 783, 748, 693, 609,
549, 531 cm ⁻¹ ;
HRMS (FAB); [M + H] ⁺ as calculated 288.1058.
Actual value 288.1059.
Example 1-6
N- (p-chloro-benzenesulfonyl)-(E) -1-phenyl-1-propenyl-amine (E-4d).

¹ H-NMR (C ₆ D ₆ ) δ:
1.34 (d, 3H, J = 7.4 Hz), 5.45-5.55 (m, 1H), 5.75-6.05 (m, 1H),
6.80-6.85 (m, 2H), 6.85-7.00 (m, 5H), 7.43-7.50 (m, 2H);
¹³ C-NMR (C ₆ D ₆ ) δ:
13.7, 116.0, 127.9, 128.0, 128.1, 128.3, 128.4, 129.0, 129.1,
129.2, 134.5, 135.7, 138.8, 139.4;
IR (neat) 3266, 3088, 3059, 2919, 2857, 1911, 1700, 1650, 1585,
1493, 1476, 1443, 1396, 1379, 1359, 1317, 1278, 1223,
1164, 1091, 1027, 1014, 960, 883, 828, 781, 755, 700, 619,
564, 533, 482 cm ^-1 ;
HRMS (FAB); [M + H] ⁺ , calculated 308.0512.
Actual value 308.0514.
Example 1-7
N- (p-chloro-benzenesulfonyl)-(Z) -1-phenyl-1-propenyl-amine (Z-4d).

Mp. 152-155 ° C;
¹ H-NMR (CDCl ₃ ); δ:
1.54 (d, 3H, J = 6.9 Hz), 5.70 (q, 1H, J = 6.9 Hz), 6.21 (s, 1H),
7.20-7.25 (m, 3H), 7.28-7.32 (m, 2H), 7.35-7.38 (m, 2H),
7.60-7.63 (m, 2H);
¹³ C-NMR (CDCl ₃ ) δ:
13.0, 121.7, 126.7, 128.1, 128.7, 129.0, 134.8, 137.3, 138.3,
139.3;
IR (neat) 3265, 1557, 1471, 1394, 1331, 1167, 1089, 1010, 900, 824,
784, 756, 667, 642, 593, 530, 482, 419 cm ⁻¹ ;
HRMS (FAB); [M + H] ⁺ as calculated 308.0512.
Actual value 308.0524.
Example 1-8
N- (p-methoxy-benzenesulfonyl)-(E) -1- (p-methoxy-phenyl) -1-propenyl-amine (E-4e).

Mp. 95-96 ° C;
¹ H-NMR (CDCl ₃ ); δ:
1.59 (d, 3H, J = 7.6 Hz), 3.78 (s, 3H), 3,87 (s, 1H),
5.57 (q, 1H, J = 7.1 Hz), 5.90 (s, 1H), 6.77-6.80 (m, 2H),
6.93-6.96 (m, 2H), 6.97-7.01 (m, 2H), 7.73-7.76 (m, 2H);
¹³ C-NMR (CDCl ₃ ) δ:
13.9, 55.3, 55.6, 113.6, 114.0, 114.2, 127.9, 129.7, 130.2,
131.4, 133.8, 159.4, 163.0;
IR (neat) 3263, 2975, 2939, 2839, 1671, 1596, 1555, 1510, 1498,
1459, 1441, 1418, 1377, 1356, 1315, 1260, 1176, 1150,
1088, 1026, 941, 881, 835, 803, 761, 739, 677, 628, 596,
552 cm ⁻¹ ;
HRMS (FAB); As E [M + H] ⁺ , calculated value 334.1113.
Actual value 334.1102.
Example 1-9
N- (p-methoxy-benzenesulfonyl)-(Z) -1- (p-methoxy-phenyl) -1-propenyl-amine (Z-4e).

Mp. 151.5-152 ° C;
¹ H-NMR (CDCl ₃ ); δ:
1.45 (d, 3H, J = 7.1 Hz), 3.78 (s, 3H), 3.84 (s, 3H),
5.50 (q, 1H, J = 7.0 Hz), 5.96 (s, 1H), 6.75-6.80 (m, 2H),
6.85-6.90 (m, 2H), 7.26-7.33 (m, 2H), 7.60-7.67 (m, 2H);
¹³ C-NMR (CDCl ₃ ) δ:
12.7, 55.2, 55.6, 113.4, 113.9, 118.4, 128.0, 129.4, 130.3,
135.0, 159.5, 163.0;
IR (neat) 3266, 1610, 1594, 1573, 1553, 1508, 1455, 1387, 1331,
1265, 1176, 1160, 1093, 1029, 824, 803, 702, 6116,
556, 419 cm ⁻¹ ;
HRMS (FAB); As [M + H] ⁺ , calculated value 334.1113.
Actual value 334.1102.
Example 1-10
N- (p-methoxy-benzenesulfonyl)-(E) -1- (p-chloro-phenyl) -1-propenyl-amine (E-4f).

Mp. 116-117 ° C;
¹ H-NMR (CDCl ₃ ); δ:
1.58 (d, 3H, J = 7.4 Hz), 3.86 (s, 3H), 5.59 (q, 1H, J = 7.2 Hz),
6.05 (s, 1H), 6.92 (d, 2H, J = 8.8 Hz), 7.01 (d, 2H, J = 8.2 Hz),
7.22 (d, 2H, J = 8.2 Hz), 7.68 (d, 2H, J = 8.8 Hz);
¹³ C-NMR (CDCl ₃ ) δ:
13.9, 55.6, 114.0, 116.8, 128.4, 129.6, 130.4, 131.1, 133.2,
133.8, 134.1, 163.1;
IR (neat) 3648, 3262, 2942, 2840, 1653, 1595, 1578, 1496, 1440,
1378, 1357, 1312, 1261, 1223, 1180, 1158, 1091, 1025,
961, 881, 833, 766, 720, 669, 628, 577, 555, 486 cm ⁻¹ ;
HRMS (FAB); As [M + H] ⁺ , calculated value 338.0618.
Actual value 338.0602.
Example 1-11
N- (p-methoxy-benzenesulfonyl)-(Z) -1- (p-chloro-phenyl) -1-propenyl-amine (Z-4f)

Mp. 175-176 ° C;
¹ H-NMR (CDCl ₃ ); δ:
1.47 (d, 3H, J = 6.9 Hz), 3.86 (s, 3H), 5.62 (q, 1H, J = 6.9 Hz),
6.02 (s, 1H), 6.87-6.90 (m, 2H), 7.19-7.22 (m, 2H),
7.28-7.32 (m, 2H) 7.60-7.63 (m, 2H);
¹³ C-NMR (CDCl ₃ ) δ:
12.8, 55.6, 114.0, 120.9, 128.1, 128.2, 129.4, 131.2, 133.8,
134.5, 136.2, 163.1;
IR (neat) 3238, 1594, 1576, 1486, 1455, 1402, 1320, 1304, 1264,
1154, 1090, 1019, 822, 802, 739, 695, 679, 608, 561,
536, 420 cm ⁻¹ ;
HRMS (FAB); As [M + H] ⁺ , calculated value 338.0618.
Actual value 338.0612.
Example 1-12
N- (p-methoxy-benzenesulfonyl)-(E) -1-phenyl-1-butenyl-amine (E-4g).

¹ H-NMR (C ₆ D ₆ ) δ:
0.72 (t, 3H, J = 7.5 Hz), 1.83 (quintet, 2H, J = 7.6 Hz),
3.05 (s, 3H), 5.61 (t, 1H, J = 7.8 Hz), 6.48-6.52 (m, 2H),
6.92-6.97 (m, 4H), 7.73-7.77 (m, 2H);
¹³ C-NMR (C ₆ D ₆ ) δ:
14.5, 21.6, 54.6, 113.7, 113.9, 121.5, 127.6, 128.0, 128.9,
129.4, 129.8, 132.4, 133.6, 136.3, 162.7;
IR (neat) 3267, 2963, 2930, 2871, 1595, 1578, 1497, 1444, 1362,
1317, 1260, 1217, 1180, 1155, 1091, 1025, 923, 886,
834, 803, 775, 700, 628, 579, 553 cm ^-1 ;
HRMS (FAB); [M + H] ⁺ as calculated 318.1164.
Actual value 318.1161.
Example 1-13
N- (p-methoxy-benzenesulfonyl)-(Z) -1-phenyl-1-butenyl-amine (Z-4g).

Mp. 170-171 ° C;
¹ H-NMR (CDCl ₃ ); δ:
0.83 (t, 3H, J = 7.5 Hz), 1.89 (quintet, 2H, J = 7.5 Hz),
3.84 (s, 3H), 5.50 (t, 1H, J = 7.4 Hz), 6.03 (s, 1H),
6.84-6.90 (m, 2H), 7.21-7.27 (m, 3H), 7.33-7.38 (m, 2H),
7.58-7.65 (m, 2H);
¹³ C-NMR (CDCl ₃ ) δ:
13.4, 20.8, 55.6, 113.8, 126.9, 127.8, 128.0, 129.5, 131.3,
133.8, 137.6, 163.0;
IR (neat) 3237, 2966, 1595, 1577, 1498, 1443, 1411, 1322, 1303,
1265, 1183, 1158, 1094, 1022, 920, 848, 802, 767, 739,
694, 624, 550 cm ^-1 ;
HRMS (FAB); [M + H] ⁺ as calculated 318.1164.
Actual value 318.1162.
Example 1-14
N- (p-methoxy-benzenesulfonyl)-(E) -2-penten-1-yl-amine (E-4h).

Mp. 85-86 ° C;
¹ H-NMR (C ₆ D ₆ ) δ:
0.78 (t, 3H, J = 7.3 Hz), 1.29 (d, 3H, J = 6.9 Hz),
1.94 (t, 2H, J = 7.3 Hz), 1.93 (q, 2H, J = 7.8 Hz), 3.06 (s, 3H),
5.34-5.46 (m, 1H), 6.50-6.80 (m, 3H), 7.85-7.98 (m, 2H);
¹³ C-NMR (C ₆ D ₆ ) δ:
11.9, 12.2, 23.3, 54.9, 111.1, 114.1, 130.0, 132.3, 136.6, 163.0;
IR (neat) 3267, 2974, 2841, 1596, 1579, 1499, 1461, 1442, 1414,
1320, 1260, 1181, 1156, 1094, 1058, 1024, 954, 891, 833,
803, 681, 628, 593, 566, 546 cm ⁻¹ ;
HRMS (FAB); [M + H] ⁺ as calculated 256.1007.
Actual value 256.1017.

Since this crystal was suitable for the measurement of X-ray diffraction, it was recrystallized from AcOEt / hexane and analyzed. This data can be obtained free of charge as CCDC-629329 by accessing www.ccdc.cam.ac.uk/conts/retrieving.htmlam.ac.uk/conts/retrieving.html.
Example 1-15
N- (p-methoxy-benzenesulfonyl)-(Z) -2-penten-1-yl-amine (Z-4h).

Mp. 101-102 ° C;
¹ H-NMR (CDCl ₃ ); δ:
0.97 (t, 3H, J = 7.3 Hz), 1.30 (d, 3H, J = 6.9 Hz),
2.16 (q, 2H, J = 7.5 Hz), 3.86 (s, 3H), 5.03 (q, 1H, J = 6.9 Hz),
5.70-5.83 (m, 1H), 6.93-6.97 (m, 2H), 7.75-7.80 (m, 2H);
¹³ C-NMR (CDCl ₃ ) δ:
11.7, 12.1, 27.9, 55.6, 114.1, 115.0, 129.2, 131.8, 136.6, 162.9;
IR (neat) 3275, 2969, 2938, 2841, 1671, 1596, 1578, 1498, 1461,
1442, 1396, 1321, 1260, 1180, 1156, 1094, 1063, 1024,
957, 900, 834, 803, 750, 718, 675, 629, 595, 556,
458 cm ⁻¹ ;
HRMS (FAB); [M + H] ⁺ as calculated 256.1007.
Actual value 256.1013.

Since this crystal was suitable for the measurement of X-ray diffraction, it was recrystallized from AcOEt / hexane and analyzed. This data can be obtained free of charge as CCDC-629331 by accessing www.ccdc.cam.ac.uk/conts/retrieving.htmlam.ac.uk/conts/retrieving.html.
Example 1-16
N- (p-methoxy-benzenesulfonyl) -1-cyclohexen-1-yl-amine (4i).

Mp. 86-88 ° C;
¹ H-NMR (C ₆ D ₆ ) δ:
1.10-1.40 (m, 4H), 1.72-2.02 (m, 4H), 3.03-3.25 (m, 3H),
5.51-5.70 (m, 1H), 6.50-6.70 m, 2H), 7.08 (s, 1H),
7.85-8.10 (m, 2H);
¹³ C-NMR (C ₆ D ₆ ) δ:
21.9, 22.6, 24.3, 28.2, 55.0, 113.8, 114.3, 130.0, 132.4,
133.1, 163.0, 163.1;
IR (neat) 3346, 3259, 1597, 1577, 1499, 1457, 1324, 1301, 1264,
1154, 1095, 1027, 896, 836, 568, 543 cm ⁻¹ ;
HRMS (FAB); [M + H] ⁺ as calculated 268.1007.
Actual value 268.1012.

Prepared from copper perchlorate (CuClO ₄ • 4CH ₃ CN) and chiral diamine ligand 5 (a compound in which both aryl groups in N, N′-bisaryl-cyclohexyldiimine are 4-bromophenyl groups) Addition reaction of enesulfonamide to ethyl glyoxylate using a chiral copper catalyst The method of Example 2 is shown by the following chemical reaction formula.

(1) To a container containing CuClO ₄ .4CH ₃ CN (3.3 mg, 0.010 mmol), a solution of ligand 5 (5.0 mg, 0.011 mmol) in methylene chloride (1.5 mL) was added for 12 hours. Stir. After cooling to 0 ° C., ethyl glyoxylate (40 ml, 0.40 mmol) and methylene chloride (1.5 mL) were added. Furthermore, enesulfonamide Z-4e (0.20 mmol) was added and stirred at 0 ° C. for 24 hours. Saturated aqueous sodium hydrogen carbonate solution was added to stop the reaction. The reaction solution was returned to room temperature and extracted with methylene chloride. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure.
(2) Ethanol (0.5 mL) and 48% HBr aqueous solution (0.5 mL) were added to the obtained residue, and the mixture was stirred at room temperature for 2 minutes, and then saturated sodium hydrogen carbonate aqueous solution was added at 0 ° C. to stop the reaction. The reaction solution was returned to room temperature and extracted with methylene chloride. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The crude product is purified by silica gel column chromatography

The compound 7 (compound which hydrolyzed the product 6 in the above-mentioned chemical reaction formula) represented by this was obtained. Yield 93%. The optical purity of the main diastereomer was 98% ee as a result of HPLC analysis.
(2S) -2-Hydroxy-4- (4-methoxy-phenyl) -3-methyl-4-oxo-butanoic acid ethyl ester (mixture of syn and anti isomers):
¹ H-NMR syn form (CDCl ₃ ) δ:
1.28 (t, 3H, J = 7.1 Hz), 1.29 (d, 3H, J = 7.1 Hz),
3.35 (br, 1H), 3.84-3.96 (m, 4H), 4.27 (q, 2H, J = 7.1 Hz),
4.58 (t, 1H, J = 4.2 Hz), 6.96 (apparent d, 2H, J = 9.0 Hz),
7.30-7.45 (m, 5H), 7.95 (apparent d, 2H, J = 8.8 Hz);
Anti-body (CDCl ₃ ) δ:
1.19 (t, 3H, J = 7.1 Hz), 1.36 (d, 3H, J = 7.3 Hz),
3.75 (d, 1H, J = 9.3 Hz), 3.88 (s, 3H),
3.94 (dq, 1H, J = 4.6, 7.3 Hz),
4.15 (apparent dq, 2H, J = 3.2, 7.1 Hz),
4.36 (dd, 1H, J = 4.6, 9.3 Hz), 6.92-6.99 (m, 2H),
7.90-7.97 (m, 2H);
¹³ C-NMR syn form (CDCl ₃ ) δ:
12.3, 14.0, 43.7, 55.4, 61.8, 71.7, 113.9, 128.5, 130.7, 163.7,
173.1, 200.4;
Anti-body (CDCl ³ ) δ:
14.0, 14.6, 43.2, 55.5, 61.4, 73.4, 113.9, 128.7, 130.8, 163.8,
173.2, 201.9;
IR (neat) thin body: 3477, 2979, 2935, 2850, 1730, 1670, 1600, 1573,
1510, 1463, 1420, 1308, 1261, 1173, 1125,
1027, 976, 843, 770, 604;
Anti: 3478, 2979, 2941, 2843, 1738, 1671, 1599,
1580, 1510, 1457, 1419, 1370, 1308, 1257,
1216, 1172, 1092, 1026, 974, 841 cm ^-1 ;
HRMS (FAB); as C ₁₄ H ₁₉ O ₅ [M + H] ⁺
Calculated value 267.1232.
Actual value 2677.132. ;
HPLC, Daicel Chiralcel ADH, hexane / i-PrOH = 4/1
Flow rate = 0.2 mL / min:
tR = 60.5 minutes (2R, 3R),
tR = 65.4 minutes (2S, 2S),
tR = 75.2 minutes (2R, 3S),
tR = 78.9 minutes (2S, 3R).

  It carried out similarly using the various enesulfonamides produced in Example 1 described above. These results are shown in the following Table 1 and show physical property data of the product.

(2S) -2-Hydroxy-3-methyl-4-oxo-4-phenyl-butanoic acid ethyl ester (mixture of syn and anti isomers):
¹ H-NMR syn form (CDCl ₃ ) δ:
1.26 (t, 3H, J = 7.0 Hz), 1.29 (d, 3H, J = 7.0 Hz), 3.28 (br, 1H),
3.93 (dq, 1H, J = 4.2, 7.0 Hz), 4.25 (q, 2H, J = 7.0 Hz),
4.58 (d, 1H, J = 4.2 Hz), 7.40-7.65 (m, 3H), 7.90-8.05 (m, 2H);
Anti body
anti (CDCl ₃ ) δ:
1.20 (t, 3H, J = 7.1 Hz), 1.36 (d, 3H, J = 7.3 Hz),
3.61 (d, 1H, J = 8.3 Hz), 3.98 (dq, 1H, J = 4.6, 7.1 Hz),
4.10-4.25 (m, 2H), 4.39 (dd, 1H, J = 4.6, 8.3 Hz),
7.40-7.65 (m, 3H);
¹³ C-NMR syn form (CDCl ₃ ) δ:
12.1, 14.0, 44.3, 61.9, 71.6, 128.4, 128.7, 133.3, 135.7,
173.1, 201.6;
Anti-body (CDCl ₃ ) δ:
14.0, 14.1, 44.0, 61.5, 73.1, 128.3, 128.7, 133.4, 135.9, 173.1;
IR (neat) Syn: 3480, 3063, 2978, 2936, 1734, 1678, 1596, 1579,
1449, 1369, 1217, 1133, 1062, 1023, 1001, 975,
952, 862, 794, 708;
Anti: 3481, 3059, 2981, 2941, 1738, 1685, 1588,
1454, 1372, 1255, 1209, 1144, 1092, 1024,
973, 701 cm ⁻¹ ;
HRMS (FAB); as C ₁₃ H ₁₇ O ₄ [M + H] ⁺
Calculated value 237.1127.
Actual value 237.1118. ;
HPLC, Daicel Chiralcel AS + ADH + AD,
Hexane / i-PrOH = 4/1, flow rate = 0.5 mL / min:
tR = 46.7 minutes (2S, 3S),
tR = 50.6 minutes (2R, 3R),
tR = 54.3 minutes (2S, 3R),
tR = 61.9 minutes (2R, 3S).

(2S) -4- (4-Chloro-phenyl) -2-hydroxy-3-methyl-4-oxo-butanoic acid ethyl ester (mixture of syn and anti isomers):
¹ H-NMR syn form (CDCl ₃ ) δ:
1.26 (t, 3H, J = 7.0 Hz), 1.28 (d, 3H, J = 7.0 Hz), 3.27 (brs, 1H),
3.87 (dq, 1H, J = 4.4, 7.0 Hz), 4.25 (q, 2H, J = 7.0 Hz),
4.55 (d, 1H, J = 4.4 Hz), 7.40-7.55 (m, 2H), 7.84-7.97 (m, 2H);
Anti-body (CDCl ₃ ) δ:
1.21 (t, 3H, J = 7.1 Hz), 1.34 (d, 3H, J = 7.1 Hz),
3.53 (d, 1H, J = 8.2 Hz), 3.91 (dq, 1H, J = 5.0, 7.1 Hz),
4.08-4.24 (m, 2H), 4.38 (dd, 1H, J = 5.0, 8.2 Hz),
7.42-7.52 (m, 2H), 7.80-7.95 (m, 2H);
¹³ C-NMR syn form (CDCl ₃ ) δ:
12.1, 14.0, 44.4, 62.0, 71.5, 129.0, 129.8, 134.1, 139.7, 173.1,
200.3;
Anti-body (CDCl ₃ ) δ:
13.9, 14.0, 44.1, 61.6, 73.0, 129.0, 129.8, 134.3, 139.9, 173.0,
201.8;
IR (neat) Thin body: 3485, 2982, 2938, 1730, 1682, 1589, 1571, 1488,
1455, 1401, 1217, 1132, 1092, 1013, 977, 843,
758, 692, 533, 478;
Anti: 3478, 3092, 2982, 2935, 1738, 1686, 1589,
1455, 1402, 1255, 1208, 1144, 1092, 1022,
976, 842, 751, 527 cm ^-1 ;
HRMS (FAB); as C ₁₃ H ₁₆ ClO ₄ [M + H] ⁺
Calculated value 271.0737.
Actual value 271.0745. ;
HPLC, Daicel Chiralcel AS, hexane / i-PrOH = 4/1
Flow rate = 0.5 mL / min:
tR = 15.1 minutes (2S, 3S),
tR = 16.6 minutes (2S, 3R),
tR = 21.4 minutes (2R, 3S),
tR = 23.9 min (2R, 3R).

(2S) -3-Benzoyl-2-hydroxy-pentanoic acid ethyl ester (mixture of syn and anti isomers):
¹ H-NMR syn form (CDCl ₃ ) δ:
0.93 (t, 3H, J = 7.5 Hz), 1.19 (t, 3H, J = 7.1 Hz),
1.70-2.05 (m, 2H), 3.18 (brs, 1H), 3.83 (dt, 1H, J = 5.3, 8.3 Hz),
4.19 (q, 2H, J = 7.1 Hz), 4.51 (d, 1H, J = 5.3 Hz),
7.42-7.54 (m, 2H), 7.54-7.62 (m, 1H), 7.90-8.02 (m, 2H);
Anti-body (CDCl ₃ ) δ:
1.04 (t, 3H, J = 7.6 Hz), 1.15 (t, 3H, J = 7.1 Hz),
1.80-1.95 (m, 2H), 3.70 (d, 1H, J = 9.5 Hz),
3.83 (dt, 1H, J = 4.2, 7.1 Hz), 4.09 (q, 2H, J = 7.1 Hz),
4.43 (dd, 1H, J = 4.2, 9.5 Hz), 7.46-7.52 (m, 2H),
7.56-7.63 (m, 1H), 7.88-7.95 (m, 2H);
¹³ C-NMR syn form (CDCl ₃ ) δ:
12.0, 13.9, 21.3, 51.2, 61.9, 71.1, 128.3, 128.6, 133.2, 137.0,
173.6, 201.5;
Anti-body (CDCl ₃ ) δ:
12.0, 13.9, 22.3, 50.1, 61.4, 71.3, 128.3, 128.7, 133.5, 136.6,
173.4, 203.9;
IR (neat) syn form: 3477, 2972, 2876, 1738, 1675, 1596, 1447, 1372,
1255, 1220, 1118, 1023, 931, 849, 779, 701;
Anti: 3485, 3062, 2966, 2941, 2875, 1738, 1682,
1596, 1579, 1448, 1368, 1268, 1208, 1134,
1100, 1028, 914, 849, 785, 699 cm ⁻¹ ;
HRMS (FAB); as C ₁₄ H ₁₉ O ₄ [M + H] ⁺
Calculated value 251.1283.
Actual value 251.1277. ;
HPLC, Daicel Chiralcel AS, hexane / i-PrOH = 4/1
Flow rate = 0.5 mL / min:
tR = 13.7 minutes (2S, 3S),
tR = 15.3 minutes (2S, 3R),
tR = 17.6 minutes (2R, 3R),
tR = 23.1 minutes (2R, 3S).

(2S) -2-Hydroxy-3-methyl-4-oxo-hexanoic acid ethyl ester (mixture of syn and anti isomers):
¹ H-NMR anti-isomer (C ₆ D ₆ ) δ:
0.89 (t, 3H, J = 7.1 Hz), 0.99 (d, 3H, J = 7.2 Hz),
1.97-2.08 (m, 2H), 2.70 (dq, 1H, J = 4.9, 7.2 Hz),
3.39 (d, 1H, J = 6.7 Hz), 3.80-4.00 (m, 2H),
4.11 (dd, 1H, J = 4.9, 6.7 Hz);
Thin body (C ₆ D ₆ ) δ:
0.87 (t, 3H, J = 7.1 Hz), 0.93 (t, 3H, J = 7.3 Hz),
1.02 (d, 3H, J = 7.2 Hz), 1.95-2.22 (m, 2H),
2.65 (dq, 1H, J = 4.4, 7.2 Hz), 3.05-3.23 (m, 1H),
3.80-4.00 (m, 2H), 4.38-4.47 (m, 1H);
¹³ C-NMR anti-isomer (CDCl ₃ ) δ:
7.58, 12.8, 14.0, 34.6, 49.4, 61.3, 73.0, 173.5, 211.3;
Thin body (C ₆ D ₆ ) δ:
7.7, 11.0, 14.0, 34.0, 49.5, 61.6, 71.7, 173.7, 209.9;
IR (neat) Anti: 3484, 2981, 2940, 1739, 1716, 1459, 1409, 1375,
1268, 1209, 1108, 1066, 1025, 975, 862, 808,
748;
Thin body: 3488, 2981, 2940, 1733, 1716, 1459, 1373, 1218,
1145, 1025, 977, 862, 800, 752 cm ⁻¹ ;
HRMS (FAB); as C ₉ H ₁₇ O ₄ [M + H] ⁺
Calculated value 189.1127.
Actual value 189.1120. ;

(1S) -Hydroxy- (2-oxo-cyclohexyl) -acetic acid ethyl ester (mixture of syn and anti isomers):
¹ H-NMR anti-form ((1S, 1′R), (C ₆ D ₆ ) δ:
0.95 (t, 3H, J = 7.1 Hz), 0.94-1.20 (m, 2H), 1.30-1.42 (m, 2H),
1.56-1.84 (m, 3H), 2.02-2.12 (m, 1H), 2.60-2.70 (m, 1H),
3.35 (d, 1H, J = 7.2 Hz), 3.84 (dd, 1H, J = 3.2, 7.2 Hz),
4.02 (dq, 2H, J = 1.9, 7.1 Hz);
Thin body (characteristic peak of thin body) δ:
0.88 (t, 3H, J = 7.1 Hz), 2.12-2.21 (m, 1H), 2.48-2.57 (m, 1H),
2.94 (d, 1H, J = 5.0 Hz), 4.60 (dd, 1H, J = 3.2, 5.0 Hz);
¹³ C-NMR anti-isomer (CDCl ₃ ) δ:
14.1, 24.8, 26.9, 30.1, 42.0, 53.7, 61.6, 71.1, 173.4, 211.2;
Thin body (characteristic peak of thin body) δ:
14.2, 24.6, 27.1, 41.9, 53.8, 61.7, 69.2, 173.6, 210.4;
HRMS (FAB); as C ₁₀ H ₁₇ O ₄ [M + H] ⁺
Calculated value 2011.127.
Actual value 2011.127. ;

  It carried out similarly to Example 2 according to the reaction formula shown next.

The physical properties of the product are as follows.
(2S, 3R) -2-Hydroxy-3-methyl-1,4-diphenylbutane-1,4-dione (Syn-10):
[Α] ²² _D +80.1 (69% ee, c 1.285, CHCl ₃ );
¹ H-NMR (CDCl ₃ ) δ:
1.12 (d, 3H, J = 6.9 Hz), 3.72 (d, 1H, J = 6.4 Hz),
3.83 (dq, 1H, J = 3.7, 6.9 Hz), 5.47 (dd, 1H, J = 3.7, 6.4 Hz),
7.45-7.67 (m, 6H), 7.89 (d, 2H, J = 7.3 Hz),
7.94 (d, 2H, J = 7.3 Hz);
¹³ C-NMR (CDCl ₃ ) δ:
10.4, 44.9, 73.5, 128.2, 128.6, 128.8, 129.0, 133.1, 134.0,
134.3, 136.3, 200.4, 201.3;
IR (neat) 3448, 2925, 1681, 1596, 1578, 1448, 1252, 1219, 971,
701 cm ⁻¹ ;
HRMS (FAB); as [M + H] ⁺
Calculated value 269.1178.
Measured value 269.1166;
Chiral HPLC; Daicel Chiralcel AD-H;
Hexane / i-PrOH = 4/1, flow rate = 1.0 mL / min:
tR = 9.6 minutes (2S, 3R),
tR = 13.1 minutes (2R, 3S).

(2S, 3S) -2-hydroxy-3-methyl-1,4-diphenylbutane-1,4-dione (anti-10):
[Α] ²² _D +76.5 (78% ee, c 0.685, CHCl ₃ );
¹ H-NMR (CDCl ₃ ) δ:
1.35 (d, 3H, J = 7.3 Hz), 3.95-4.04 (m, 1H), 4.37 (s, 1H),
5.20 (d, 1H, J = 4.1 Hz), 7.42-7.50 (m, 4H), 7.54-7.62 (m, 2H),
7.92 (d, 2H, J = 7.3 Hz), 7.98 (d, 2H, J = 7.3 Hz);
¹³ C-NMR (CDCl ₃ ) δ:
14.9, 42.7, 76.6, 128.4, 128.6, 128.7, 129.1, 133.5, 133.7, 135.1,
136.1, 200.2, 204.7;
IR (neat) 3069, 2929, 1682, 1595, 1448, 1218, 974, 838, 702,
420 cm ⁻¹ ;
HRMS (FAB); as [M + H] ⁺
Calculated value 269.1178.
Measured value 269.1183;
Chiral HPLC; Daicel Chiralcel AS-H;
Hexane / i-PrOH = 4/1, flow rate = 1.0 mL / min:
tR = 9.1 minutes (2S, 3S),
tR = 22.9 minutes (2R, 3R).

  According to the following reaction formula, it carried out as follows.

A toluene solution (1.5 mL) of diamine ligand 11 (9.9 mg, 0.022 mmol) was added to a container containing Cu (OTf) ₂ (7.2 mg, 0.02 mmol), and the mixture was stirred at room temperature for 12 hours. After cooling to −20 ° C., MS 3A (20 mg), toluene solution of diisopropyl azodicarboxylate (0.2 mmol) and toluene of enesulfonamide (E-4b) (0.2 mmol) prepared in Example 1 Solution (1.2 mL) was added sequentially. Furthermore, after stirring for 4.5 hours at that temperature, a saturated aqueous sodium hydrogen carbonate solution was added to stop the reaction. The reaction solution was returned to room temperature and extracted with methylene chloride. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. EtOH (0.5 mL) and 48% HBr aqueous solution (0.5 mL) were added to the obtained residue, and the mixture was stirred at room temperature for 1.5 minutes, and then saturated sodium bicarbonate aqueous solution was added at 0 ° C. to stop the reaction. The reaction solution was returned to room temperature and extracted with methylene chloride. After drying over anhydrous sodium sulfate, the desiccant was filtered off and the solvent was distilled off under reduced pressure. The crude product was purified by silica gel column chromatography to give 12. Yield 47 mg, yield 70%. The optical purity was 91% ee as a result of HPLC analysis.

Diisopropyl N- (1-methyl-2-oxo-2-phenylethyl) -N, N′-hydrazine dicarboxylic acid:
[Α] ²⁴ _D -20.1 (95% ee, c 3.46, CHCl ₃ );
_{^{1 H-NMR (CDCl 3)}} See below. ;

13C NMR (CDCl3) See bellow. ;

IR (neat) 3314, 2982, 2938, 1692, 1596, 1453, 1380, 1299, 1222, 1180,
1145, 1108, 1058, 1037, 1003, 966, 936, 766, 700 cm ⁻¹ ;
HRMS (FAB); as C ₁₇ H ₂₅ N ₂ O ₅ [M + H] ⁺
Calculated value 337.1763.
Actual value 337.1761. ;
Chiral HPLC; Daicel Chiralcel AD-H; Hexane / i-PrOH = 4/1
Flow rate = 1.0 mL / min:
tR = 8.0 minutes (R),
tR = 11.0 minutes (S).

  According to the following reaction formula, the sulfonylimine produced in Example 2 was hydrolyzed under the conditions shown in Table 2 below.

  The reaction conditions and results are shown in Table 2 below.

  According to the following reaction formula, the sulfonylimine produced in Example 2 was reduced.

  The target compounds 9a and 9b were obtained with a yield of 93%. The ratio of 9a and 9b was 92: 8.

  The present invention is an optical activity to be a raw material for optically active 1,3-amino alcohols and 1,3-carbonyl alcohols useful as raw materials and synthetic intermediates for the production of pharmaceuticals, agricultural chemicals, fragrances, functional polymers and the like. It provides a method for producing sulfonylimine with high yield and high optical yield, and is extremely useful for industries in the field of producing chemical substances, particularly in the field of fine chemicals. have.

Claims (4)

The following general formula (1)

(In the formula, R ¹ and R ² each independently represent a hydrogen atom or an alkyl group which may have a substituent, and R ³ has an alkyl group or a substituent which may have a substituent. R ⁴ represents an aryl group which may have a substituent, and R ² and R ³ together with adjacent carbon atoms have 5 to 15 carbon atoms. A ring may be formed.)
An enesulfonamide represented by the following general formula (2):

(In the formula, R ⁵ represents a —C (═O) —R ^a group or a —COO—R ^a group, and R ^a represents a hydrocarbon group which may have ^a substituent.)
A compound having an aldehyde group represented by the following formula: a copper compound and the following general formula:

(In the formula, each R independently represents a linear or branched alkyl group having 1 to 20 carbon atoms, or an aryl group having 6 to 26 carbon atoms which may have a substituent.)
And a diimine containing an asymmetric carbon atom represented by the following general formula (3):

(In the formula, R ¹ and R ² each independently represent a hydrogen atom or an alkyl group which may have a substituent , and R ³ has an alkyl group or a substituent which may have a substituent. represents an aryl group which may be, R ⁴ represents an aryl group which may have a substituent, and the carbon of 5 to 15 carbon atoms together with the carbon atoms to which R ² and R ³ are adjacent, together A ring may be formed, and R ⁵ represents a —C (═O) —R ^a group or a —COO—R ^a group, and R ^a represents a hydrocarbon group which may have ^a substituent . )
A process for producing a sulfonylimine compound represented by the formula: 2. The method according to claim 1 , wherein the diimine containing an asymmetric carbon atom is an optically active substance, and the sulfonylimine compound represented by the general formula (3) to be produced contains at least one optically active substance in excess. The method according to claim 1 or 2 , wherein the sulfonylimine compound represented by the general formula (3) is an optically active substance. The method according to any one of claims 1 to 3 , wherein the copper compound is copper perchlorate.