JP2003261490A - NEW CHIRAL ZIRCONIUM CATALYST AND METHOD FOR PRODUCING OPTICALLY ACTIVE ANTI-alpha-METHYL-beta-AMINOCARBONYL COMPOUND - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing an α-methyl-β-aminocarbonyl compound in high anti-selectivity and in high enanthio selectivity. <P>SOLUTION: This method for producing the α-methyl-β-aminocarbonyl compound comprises reacting an imine with a silicon enolate in the presence of a new chiral zirconium catalyst represented by formula (I) (X is an electron- attracting group). <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel chiral zirconium catalyst and an optically active anti-α-containing the same.
The present invention relates to a method for producing a methyl-β-aminocarbonyl compound. More specifically, the invention of this application relates to a novel chiral zirconium catalyst and a highly anti- and highly enantioselective asymmetric Mannich type reaction method for anti-selectively producing an α-methyl-β-aminocarbonyl compound. It is about.

[0002]

[Prior art and its problems] Macrolides, polyethers,
Since many biologically important compounds such as carbohydrates have α-methyl-β-hydroxy moieties, there have been many asymmetric reaction methods to synthesize compounds containing such moieties. Has been reported. For example, asymmetric aldol reaction (Carreira, EM, Comprehe
nsive Asymmetric Catalysis; Jacobsen, EN, Pfalt
z, A., Yamamoto, Y., Eds .; Springer: Heidelberg, 1
999, Vol. 3, p 988) is mentioned as a particularly important asymmetric synthesis method.

On the other hand, the α-methyl-β-amino moiety as the corresponding aza compound is also nodularin (Rinehart, KL, H
arada, K., Namikoshi, M., Chen, C., Harvis, CA,
Munro, MHG, Blunt, JW, Mulligan, PE, Beasle
y, VR, Dahlem, AM, Carmichael, WWJAm.Chem.
Soc., 1988, 110, 8557), onchidin (Rodriguez, J.,
Fernandez, R., Quinoa, E., Riguera, R., Debitus,
C., Bouchet, P. Tetrahedron Lett. 1994, 35, 923
9), and majusculamide C (Carter, DC, Moore,
RE, Mynderse, JS, Niemezura, WP, Todd, JS
J.Org.Chem. 1984,49,236) and other natural substances such as marine bioactive peptides, and is considered to be an important compound in the synthesis of peptidomimetics (Xie, J., Solei
lhac, J.-M., Schmidt, C., Peyroux, J., Roques, B.
P., Fournie-Zaluski, M.-CJMed.Chem. 1989, 32, 1
497; Seebach, D., Abele, S., Gademann, K., Guichar
d, G., Hintermann, T., Jaun, B., Matthews, JL, S
chreiber, JV, Oberer, L., Hommel, U., Widmer, Han
s. Helv. Chim. Acta 1998, 81, 932), and also as a synthetic intermediate for β-lactamines which are candidate compounds of pharmacologically active substances (eg Wang, W.-B., Roskam.
p, EJJAm.Chem.Soc. 1993, 115, 9417, etc.). However, the reality is that methods for synthesizing these chemical moieties with high enantioselectivity were limited.

For example, β-amino acids and α-substituted β-
Enantioselective Synthesis of Amino Acids
of β-Amino Acids; Juraisti, E., Ed., Wiley-VCH,
Weinheim, 1997; Jauristi, El, Quintana, D., Escala
nte, J. Aldrichim.Acta 1994, 27, 3; Cole, DC Tet
rahedron 1994, 50, 9517; Cardillo, G., Tomasini, C.
Chem.Soc.Rev. 1996, 117), asymmetric synthesis of α-alkyl-β-aminocarbonyl compounds by enolate-imine condensation (Hart, DJ, Lee, Cl-SJAm.Chem.Soc. 198).
6, 108, 6054; Gennari, C., Venturini, I., Gislon,
G., Schimperna, G. Tetrahedron Lett. 1987, 28, 22
7; Yamada, T., Suzuki, H., Mukaiyama, T. Chem. Let
1987, 28, 227 et al.), synthesis of α-alkyl-β-amino moieties from α-iminoesters by diastereo and enantioselective catalysis (Hafez, AM, Tggi,
AE, Dudding, T., Lectka, Tl J. Am. Chem. Soc. 2001,
123, 10853; Ferraris, D., Young, B., Cox, C., Dud
ding, T., Drury, WJ, III, Tyzhkov, L., Taggi,
A., Lectka, TJAm.Chem.Soc. 2002, 124, 67) have been reported. In addition, recently, direct Mann using a catalyst is used.
An ich type reaction has been reported (Yamasaki, S., Iida, T.,
Shibasaki, M. Tetrahedron 1999, 55, 8857; List, B.
Synlett 2001, 1675; Juhl, K., Gathergood, N., Jor
gensen, KA Angew.Chem., Int.Ed.Engl. 2001, 40, 29
95). Furthermore, a method for the catalytic synthesis of α- (α-aminoalkyl) acrylates by diastereoselective hydrogenation and kinetic resolution was also reported (Brown, JM, James, A.
P., Prior, LM Tetrahedron Lett. 1987, 28, 2179;
Takagi, M., Yamamoto, K. Tetrahedron 1991, 47, 886
9).

The inventors of the present application have also reported that certain chiral zirconium complexes to date serve as effective catalysts in the Mannich-type reaction of imine and silicon enolate (Ishitani, H., Ueno). , M., Kobayashi,
SJAm.Chem.Soc. 1997, 119, 7153; Kobayashi, S.,
Ishitani, H., Ueno, MJAm.Chen.Soc. 1998, 120,
431; Ishitani, H., Kitazawa, T., Kobayashi, S. Tet
rahedron Lett. 1999,40, 2161; Kobayashi, S., Kusak
abe, K., Komiyama, S., Ishitani, HJOrg.Chem. 19
99, 64, 4220; Ishitani, H., Ueno, M., Kobayashi,
S., J. Am. Chem. Soc. 2000, 122, 8180; Kobayashi, S.,
Ishitani, H., Yamashita, Y., Ueno, M., Shimizu, H.
Tetrahedron 2001, 57, 861).

However, all of these known methods have high antiselectivity and enantioselectivity of α-methyl-β-.
It has not been possible to realize the synthesis of aminocarbonyl compounds.

Therefore, the invention of this application has been made in view of the above circumstances, solves the problems of the prior art, and anti-selectively the α-methyl-β-aminocarbonyl compound, and It is an object to provide a method for producing with high enantioselectivity.

[0008]

The invention of this application is intended to solve the above-mentioned problems. First, firstly, the following formula (I) is used.

[0009]

[Chemical 5]

A novel chiral zirconium catalyst represented by the formula (wherein X is an electron-withdrawing group) is provided.

Secondly, the invention of this application is based on Zr (O ^t Br) ₄
And (R) -6,6'-XBINOL (where X is an electron-withdrawing group)
Disclosed is a novel chiral zirconium catalyst obtained by mixing N-methylimidazole with N-methylimidazole.

The invention of this application is, thirdly, a novel chiral zirconium catalyst in which X is a fluorinated hydrocarbon group, and fourthly, a novel chiral zirconium catalyst in which X is a tetrafluoroethyl group. A zirconium catalyst is provided.

A fifth aspect of the present invention is a method for antiselectively producing an optically active α-methyl-β-aminocarbonyl compound, which comprises imine and silicon enolate represented by the following formula (I):

[0014]

[Chemical 6]

A method for producing an optically active anti-α-methyl-β-aminocarbonyl compound, which comprises reacting in the presence of a chiral zirconium catalyst represented by the formula (where X is an electron-withdrawing group) is provided. To do.

The sixth aspect of the invention of this application is that the chiral zirconium catalyst comprises Zr (O ^t Br) ₄ and (R) -6,6'-XBINOL (where X is an electron-withdrawing group) and N. The method for producing an optically active anti-α-methyl-β-aminocarbonyl compound obtained by mixing -methylimidazole is as follows. Seventhly, in the chiral zirconium catalyst, X is an optically active anti-α-methyl-β-aminocarbonyl compound. Provided is a method for producing a methyl-β-aminocarbonyl compound, and eighthly, for a chiral zirconium catalyst, a method for producing an optically active anti-α-methyl-β-aminocarbonyl compound in which X is a tetrafluoroethyl group. .

Ninth, according to the invention of this application, the imine has the following formula (II):

[0018]

[Chemical 7]

(Wherein R ¹ is a hydrocarbon group which may have a substituent or an aromatic group which may have a substituent, and R ² is a hydrogen atom or a substituent. The present invention provides a method for producing any of the above-mentioned optically active anti-α-methyl-β-aminocarbonyl compounds represented by (which is a hydrocarbon group which may have).

The invention of this application is, tenth, a method for producing an optically active anti-α-methyl-β-aminocarbonyl compound in which the silicon enolate is a silicon enolate derived from phenyl propionate, and eleventh. , Silicon enolate is represented by the following formula (III)

[0021]

[Chemical 8]

A method for producing an optically active anti-α-methyl-β-aminocarbonyl compound represented by the formula (wherein R ³ is an aromatic group which may have a substituent) is also provided.

[0023]

BEST MODE FOR CARRYING OUT THE INVENTION In the invention of this application, first, an imine and a silicon enolate are represented by the following formula (I):

[0024]

[Chemical 9]

An optically active α-methyl-β-aminocarbonyl compound can be produced antiselectively by carrying out a Mannich type reaction in the presence of a novel chiral zirconium catalyst represented by:

This novel chiral zirconium catalyst (I)
Is obtained by mixing Zr (O ^t Br) ₄ and (R) -6,6′-XBINOL with N-methylimidazole in, for example, a solution,
Substituent X is selected from various electron withdrawing groups. X is
For example, halogen, CO ₂ Et, COMe, CN and the like can be mentioned.
Of these, a fluorinated hydrocarbon having a high electron-withdrawing property is preferable as X. As is clear from the examples described below, according to the research conducted by the inventors, particularly when a tetrafluoroethyl group is used, the optical purity (enantioselectivity) in the Mannich-type reaction of imine and silicon enolate becomes high,
preferable.

In the method for producing an optically active anti-α-methyl-β-aminocarbonyl compound of the invention of this application,
Various types of imines are considered, among which the following formula (II)

[0028]

[Chemical 10]

Compounds represented by are preferred. At this time,
R ¹ is appropriately selected from a hydrocarbon group which may have a substituent and an aromatic group which may have a substituent. Among them, phenyl group, substituted phenyl group, naphthyl group, substituted naphthyl group, methyl, ethyl, n-propyl, i
Preferred examples include alkyl groups such as -propyl, n-butyl, i-butyl, t-butyl, cyclohexyl groups and the like. On the other hand, R ² is a hydrogen atom or a hydrocarbon group which may have a substituent, and is alkyl such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl and t-butyl. Examples include groups. R ¹ and R ² in the starting imine may be appropriately selected depending on the desired Mannich-type reaction product, that is, the optically active anti-α-methyl-β-aminocarbonyl compound. Also,
As such an imine, a compound used as a reagent or a compound synthesized, purified, or isolated in advance may be used, but for those difficult to isolate or unstable, Mann
It may be synthesized and used in situ for the ich type reaction.

Further, in the method for producing an optically active anti-α-methyl-β-aminocarbonyl compound of the invention of this application, it is preferable that the nucleophile, silicon enolate, be derived from phenyl propionate. Specifically, silicon enolate has the following formula (III)

[0031]

[Chemical 11]

In the compound (III), R ³ is an aromatic group which may have a substituent. For example, R ³ is a phenyl group, a substituted phenyl group,
A naphthyl group, a substituted naphthyl group or the like may be appropriately selected depending on the intended optically active anti-α-methyl-β-aminocarbonyl compound. Further, such a silicon enolate may be a commercially available one, or one synthesized, purified and isolated in advance, or may be one synthesized in situ during the Mannich type reaction.

In the method for producing an optically active anti-α-methyl-β-aminocarbonyl compound of the invention of the present application as described above, the Mannich-type reaction is carried out in the presence of the above novel chiral zirconium catalyst. Often,
The reaction conditions are not particularly limited. For example, the reaction is
It is preferably carried out in various organic solvents. The solvent is
As long as it can dissolve the starting material imine, the nucleophile silicon enolate, and the catalyst, as long as it does not solidify or decompose at the reaction temperature,
There is no particular limitation. Examples include halogen-containing solvents such as chloroform and dichloromethane, acetone, and the like.
The reaction temperature may be in a temperature range in which each reactant is stable and the catalyst acts particularly stably, and is preferably a low temperature of room temperature or lower, more preferably about -100 ° C to room temperature. Furthermore, for specific reaction operations, operations such as stirring, separation, and purification that are carried out in general chemical reactions can be applied.

Hereinafter, the invention of this application will be described in more detail with reference to Examples. Needless to say, the invention of this application is not limited to the following examples.

[0035]

EXAMPLES In the following examples, melting points are shown without correction.

The ¹ H and ¹³ C NMR spectra are also based on JEOL JNM-LA300, J in CDCl ₃ unless otherwise specified.
It was measured with a NM-LA400 or JNM-LA500 spectrometer. ^{At 1} H, tetramethylsilane (TMS) was used as an internal standard (δ = 0). Also, at ¹³ C, CDC
l ₃ was used as an internal standard (δ = 77.0).

The IR spectrum was measured using a JASCO FT / IR-610 spectrometer.

Circular optical rotation was measured with a JASCO P-1010 polarimeter.

High Performance Liquid Chromatography is SHIMADZU
LC-10AT (liquid chromatograph), SHIMADZU SPD-10A
(UV detector), and SHIMADZU C-R6A or C-R8A
Performed using a Chromatopack.

Column chromatography is performed by Silica gel.
60 (Merck), and thin-layer chromatography with Wak
It was performed using ogel B-5F (Wako Pure Chemical Industries).

Dichloromethane, after distillation over P ₂ O ₅ ,
Distilled over CaH and dried over MS 4A. Other solvents and compounds were purified by standard methods before use.

The aromatic and heteroaromatic aldehyde aldimines were prepared by the general method using the corresponding aldehyde and 2-aminophenol. The crude aldimine was recrystallized from ethanol to give a pure substance. Ketene silyl acetals are prepared by known methods (Ireland,
RE; Mueller, RH; Willard, AKJAm.Chem.Soc.
1976, 98, 2826). <Example 1> of ketene silyl acetal and aldimine
Mannich reaction (1) First, based on the following formula (A), aldimine (2a)
And ketene silyl acetal (3 (E)) (E / Z = 96/4) were reacted in the presence of chiral zirconium catalyst (10 mol%) (1a).

[0043]

[Chemical 12]

At room temperature, (R) -6,6'-dibromo-1,1'-bi-2-n
To a dichloromethane (0.5 mL) solution of aphthol ((R) -6,6'-BrBINOL) (0.088 mmol), a solution of Zr (O ^t Bu) ₄ (0.04 mmol) in dichloromethane (0.25 mL) and N-methylimidazole ( A solution of 0.08 mmol) in dichloromethane (0.25 mL) was added, and the mixture was stirred for 1 hr and cooled to -45 ° C. Compound 2a
(0.4 mmol) and 3 (E) (0.48 mmol) in dichloromethane (1.5 mL each) were added in that order, stirred for 24 hours, and saturated NaHC
The reaction was stopped by adding an O ₃ aqueous solution. The aqueous layer was extracted with dichloromethane, and the crude product was separated by silica gel chromatography to give compound 4a.

The diastereomeric ratio was determined by ¹ H NMR analysis, and the optical purity was determined by HPLC analysis using a chiral column.

The yield, diastereoselectivity, and optical purity of compound 4a are shown in Table 1 (Reaction 1).

[0047]

[Table 1]

(2) The reaction temperature was set to -78 ° C, and (1)
Compound 4a was obtained by a method similar to.

The yield, diastereoselectivity, and optical purity of compound 4a are shown in Table 1 (Reaction 2). (3) Instead of a solution of ((R) -6,6'-BrBINOL) (0.088 mmol) in dichloromethane (0.5 mL), (R) -6,6'-bis (penta
A catalyst was prepared using a solution of fluoroethyl) -1,1'-bi-2-naphthol (0.088 mmol) in dichloromethane (0.5 mL),
Compound 4a was obtained by the same method as in (1).

The yield, diastereoselectivity, and optical purity of compound 4a are shown in Table 1 (reaction 3). (4) Compound 4a was synthesized in the same manner as in (3) with the reaction temperature set at -78 ° C.

The yield, diastereoselectivity, and optical purity of compound 4a are shown in Table 1 (Reaction 4). The identification results of the obtained compound 4a are shown in Table 2.

[0052]

[Table 2]

(5) The same reaction as in (4) was carried out using ketene silyl acetal (3 (Z)) (E / Z = 22/78).

The yield, diastereoselectivity, and optical purity of compound 4a are shown in Table 1 (reaction 5).

Table 1 shows that by using the catalyst of the present invention, α-methyl-β-amino ester (4a) can be obtained with high antiselectivity. Particularly, by carrying out the reaction at −78 ° C. using a chiral zirconium catalyst having a pentafluoroethyl group having a high electron withdrawing property as X, the optical purity (enantioselectivity) of the anti body was increased. <Example 2> Mannich-type reaction of various aldimines and ketene silyl acetal 3 (E) According to the following formula (B), various aldimines and ketene silyl acetals (compound 3 (E)) were prepared in the same manner as in Example 1.
A Mannich type reaction was performed. The catalyst is from Example 1 (3)-
The catalyst (I) in which X used in (5) was a tetrafluoroethyl group was used.

[0056]

[Chemical 13]

The identification results of the obtained compounds 4b to 4i are shown in Table 3 to
Shown in 10.

[0058]

[Table 3]

[0059]

[Table 4]

[0060]

[Table 5]

[0061]

[Table 6]

[0062]

[Table 7]

[0063]

[Table 8]

[0064]

[Table 9]

[0065]

[Table 10]

Table 11 shows the yield, diastereoselectivity, and optical purity of each product obtained.

[0067]

[Table 11]

In reactions f to i, aldimine was prepared in situ from the corresponding aldehyde and 2-amino-m-cresol in the presence of MS 4A.

From Table 11, the optically active anti-α of the present invention is shown.
In the method for producing a -methyl-β-aminocarbonyl compound, it has been confirmed that α-methyl-β-amino ester can be obtained antiselectively and with high enantioselectivity by using various aldimines. <Example 3> Synthesis of α-methyl-β-amino acid derivative From the α-methyl-β-amino ester (4a, 4f) obtained in Example 2, according to the following formulas (C) and (D), respectively. The corresponding α-methyl-β-amino acid derivative was obtained. (1) (2R, 3R) -Methyl-3-amino-2-methyl-3-phenylprop
Synthesis of anoate (Compound 6)

[0070]

[Chemical 14]

First, at room temperature, 4a (syn / anti = 2/98, anti =
K ₂ CO ₃ (166 mg, 1.20 mmol) was added to a MeOH (0.8 ml) solution of 92% ee) (210 mg, 0.60 mmol), stirred for 20 minutes, and then the reaction was stopped with a saturated NH ₄ Cl aqueous solution.

After filtration, the solvent was removed and crude methyl 3- (2
-Hydroxyphenyl) amino-2-methyl-3-phenylpropanoate was obtained. This was dissolved in MeI / acetone (1: 5) solution (8.0 ml), and K ₂ CO ₃ (332 mg, 2.40 mm) was added at room temperature.
ol) was added and further purified by silica gel chromatography to obtain (2R, 3S) -methyl3- (2-methoxyphen
yl) amino-2-methyl-3-phenylpropanoate (Compound 5)
(131 mg, 73%) was obtained as pure anti isomer.

The identification results are shown in Table 12.

[0074]

[Table 12]

Furthermore, the compound 5 (50 mg, 0.17 mmol)
Catalyst AgNO3 (14 mg, 0.08 mmo on H ₂ O / MeCN (1: 2, 2.8 ml)
l) was added at 60 ° C., and (NH ₄ ) ₂ S ₂ O ₈ (306 mg, 1.34 mmo
l) (Bhattarai, K; Cainelli, G .; Panunzio, M. Synl
ett 1990, 229) was gradually added over 20 minutes.

After stirring for 4 hours, the reaction solution was cooled at room temperature, diluted with water, treated with K ₂ CO ₃ until the pH reached 7 or more, and extracted with EtOAc. The crude product was purified by silica gel chromatography to obtain the target β-amino ester (Compound 6) (23 mg, 70%).

The identification results are shown in Table 13.

[0078]

[Table 13]

In Table 13, a known method (Davi
es, SG; Walters, IASJChem.Soc., Perkin Tran
s 1 1994, 1129), compound [6] prepared in [α] _D ²⁵ -2
It was 9.2 (c1.00, CHCl ₃ ). (2) (2R, 3R) -Methyl 3- (tert-butoxycarbonyl) amino-
Synthesis of 2,5-dimethylhexanoate (Compound 8)

[0080]

[Chemical 15]

At room temperature, 4f (syn / anti = 9/91, anti = 92% e
e) (127 mg, 0.37 mmol) in MeOH (5.0 ml) solution with K ₂ CO
After adding ₃ (102 mg, 0.74 mmol) and stirring for 20 minutes,
The reaction was quenched with saturated aqueous NH ₄ Cl.

After filtration, after performing general operations such as removal of the solvent, and further purification by silica gel chromatography, (2R, 3R) -methyl2,5-dimethyl-3- (2-hydroxy-
6-methylphenyl) aminohexanoate (Compound 7) (98 mg,
95%) was obtained as the pure anti-isomer.

The identification results are shown in Table 14.

[0084]

[Table 14]

Furthermore, the compound 7 (78 mg, 0.28 mmol)
The catalyst cerium ammonium nitrate (CAN) (459 mg, 0.84 mmol) was added to H ₂ O / MeCN (1: 4, 3.5 ml) at 0 ° C., and 2
After reacting for 0 minutes, the mixture was diluted with water and EtOAc, and treated with K ₂ CO ₃ until the pH became 7 or more. The insoluble matter was filtered through a Celite pad, and the aqueous layer was extracted with EtOAc. Combine organic layers, 10%
It was washed with Na ₂ CO ₃ aqueous solution and 10% Na ₂ SO ₃ aqueous solution and brine, and dried over Na ₂ SO ₄ . After filtration, remove the solvent and
(2R, 3R) -methyl 3-amino-2,5-dimethylhexanoate was obtained. Dissolve this in dichloromethane (3.0 ml) and use Boc ₂ O.
A solution of (183 mg, 0.84 mmol) in dichloromethane (0.8 ml) was added at room temperature. Stir for 4 hours, remove the solvent, purify the crude product by silica gel chromatography,
-Boc-β-amino ester (Compound 8) was obtained (33.7 m
g, 44%).

The identification results are shown in Table 15.

[0087]

[Table 15]

In Table 15, known methods (Seebach,
D .; Abele, S .; Gademann, K .; Guichard, G .; Hinterm
ann, T .; Jaun, B .; Matthews, JL; Schreiber, J.
V .; Oberer, L .; Hommel, U .; Widmer, Hans. Helv. Chi
m.Acta 1998, 81, 932), [α]
_{It was D} ²³ +23.4 (c 1.42, CHCl ₃ ). Reference Example 1 (R) -6,6'-bis (pentafluoroethyl) -1,1'-
bi-2-naphthol ((R ) -6,6'-C 2 F 5 BINOL) was used in Synthesis Example 1-2 _{(R) -6,6'-C 2 F} 5 BINOL
Was obtained by the following method.

(R) -2,2'-Bis (methoxymethyloxy) -6,6'-bi
s (pentafluoroethyl) -1,1'-binaphthyl (MOM- (R) -6,6'-
C ₂ F ₅ BINOL) is (R) -2,2'-bis (methoxymethyloxy) -6,6 '
It was synthesized using -diiodo-1,1'-binaphthyl (MOM- (R) -6,6'-IBINOL) as a raw material.

MOM- (R) -6,6'-IBINOL (3.50 g, 5.7 mmo
Saturated HCl methanol solution (8.0 ml) was added to the dichloromethane (5.0 ml) solution of (1) at 0 ° C. over 30 minutes. The resulting solution was diluted with water and extracted with dichloromethane. Combine the organic layers and wash with water and saturated aqueous NaHCO ₃ ,
Dried over ₂ SO ₄ . After removing the solvent, the residue was purified by silica gel chromatography (hexan / CH ₂ Cl ₂ = 1/2) to obtain (R) -6,6'-C ₂ F ₅ BINOL (2.87 g, 96%). It was

The identification results are shown in Table 16.

[0092]

[Table 16]

[0093]

As described in detail above, according to the invention of this application, a method for producing an optically active α-methyl-β-aminocarbonyl compound with high antiselectivity and enantioselectivity, and a novel chiral zirconium catalyst therefor are provided. Provided. The optically active anti-α-methyl-β-aminocarbonyl compound obtained by the method of the present invention is an important intermediate in the synthesis of various natural substances and physiologically active substances and is highly useful.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) C07C 229/28 C07C 229/28 229/34 229/34 231/02 231/02 233/47 233/47 / / C07B 53/00 C07B 53/00 BF 61/00 300 61/00 300 C07M 7:00 C07M 7:00 F term (reference) 4G069 AA06 BA27A BA27B BC51A BC51B BE20A BE20B BE34A BE34B CB25 CB57 CB72 4H006 AC53 AC48 AC48 AC53 AC48 AC81 BA10 BA45 BA51 BJ50 BN30 BU46 BV22 TA01 TB52 4H039 CA66 CA71 CF40 CG90 CL25

Claims (11)

[Claims] 1. The following formula (I): A novel chiral zirconium catalyst represented by the formula (where X is an electron-withdrawing group). 2. Zr (O ^t Br) ₄ and (R) -6,6'-XBINOL (however,
X is an electron-withdrawing group) and a novel chiral zirconium catalyst obtained by mixing N-methylimidazole. 3. X is a fluorinated hydrocarbon group.
Or the novel chiral zirconium catalyst of any of 2. 4. The novel chiral zirconium catalyst according to claim 3, wherein X is a tetrafluoroethyl group. 5. Anti-selectively optically active α-methyl-β
A method for producing an aminocarbonyl compound, wherein imine and silicon enolate are represented by the following formula (I): (However, X is an electron-withdrawing group.) A method for producing an optically active anti-α-methyl-β-aminocarbonyl compound, which comprises reacting in the presence of a chiral zirconium catalyst. 6. The chiral zirconium catalyst is Zr (O ^t Br) ₄
And (R) -6,6'-XBINOL (where X is an electron-withdrawing group)
And N-methylimidazole are mixed to obtain the compound.
A method for producing an optically active anti-α-methyl-β-aminocarbonyl compound. 7. The method for producing an optically active anti-α-methyl-β-aminocarbonyl compound according to claim 5, wherein in the chiral zirconium catalyst, X is a fluorinated hydrocarbon group. 8. The method for producing an optically active anti-α-methyl-β-aminocarbonyl compound according to claim 7, wherein in the chiral zirconium catalyst, X is a tetrafluoroethyl group. 9. The imine has the following formula (II): (However, R ¹ is a hydrocarbon group which may have a substituent, or an aromatic group which may have a substituent,
R ² is a hydrogen atom or a hydrocarbon group which may have a substituent), and the production of the optically active anti-α-methyl-β-aminocarbonyl compound according to any one of claims 5 to 8. Method. 10. The silicon enolate is a silicon enolate derived from phenyl propionate.
Optically active anti-α-methyl-β-
A method for producing an aminocarbonyl compound. 11. A silicon enolate is represented by the following formula (III): (Wherein, R ³ is substituted is also an aromatic group) process for producing an optically active anti α- methyl -β- aminocarbonyl compound of claim 10 which is represented by.