JP3304380B2 - Asymmetric induction catalyst - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an asymmetric induction catalyst. More specifically, the present invention relates to a catalyst useful for producing asymmetric cyanohydrin by adding hydrogen cyanide to an aldehyde compound.

[0002]

BACKGROUND OF THE INVENTION The present inventors have previously described cyclo [(S) -phenylalanyl-
(S) -histidyl], the asymmetric addition reaction of hydrogen cyanide to the aldehyde compound proceeds,
(R) -form cyanohydrin is reported to be obtained (Inoue et al., J. Chem. Soc. Chem. Commun., 229 (1981)).
Bull. Chem. Soc. Jpn., 59, 893 (1986)). For example,
By reacting benzaldehyde with hydrogen cyanide in the presence of cyclo-[(S) -phenylalanyl- (S) -histidyl], (R) -mandelonitrile can be obtained in relatively high purity and high yield. The present inventors have continued to study the asymmetric induction reaction caused by the dipeptide, and have found an even more excellent asymmetric induction catalyst, leading to the present invention.

[0003]

That is, the present invention provides a compound represented by the general formula
Chemical 3

Embedded image Wherein R ¹ is an isopropyl group, an isobutyl group,
- butyl group, tert- butyl group, a methyl group, a phenyl group or <br/> other represents a benzyl group, R ² represents benzyl or indol-3-ylmethyl group, an isopropyl group, an isobutyl group or a phenyl group, R ³ is a lower alkoxy (for example, C _1-4 alkoxy such as methoxy or ethoxy) group, a hydroxy group or a mono- or di-lower alkyl (for example, C _1-4 alkyl such as methyl or ethyl)
R ⁴ represents a hydrogen atom, or R ² and R ⁴ are bonded at a terminal to form a trimethylene group. R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and are a hydrogen atom, a halogen atom (eg, a fluorine atom, a chlorine atom, a bromine atom), a lower alkyl (eg, methyl, ethyl, propyl, isopropyl, isobutyl, sec. A C _1-4 alkyl) group such as -butyl, tert-butyl or a lower alkoxy (eg C _1-4 alkoxy) such as methoxy, ethoxy, or R ⁵ and R ⁶ ,
R ⁶ and R ⁷ , or R ⁷ and R ⁸ are bonded at the terminal to form CH ＝ CH
It represents a group represented by the group or OCH ₂ O represented by -CH = CH. * Indicates the configuration of S or R. And a method for producing cyanohydrin by the addition of hydrogen cyanide to an aldehyde compound using the catalyst. . Some embodiments of the dipeptide compound represented by the general formula 3 are shown below. (Chemical formula 4, Chemical formula 5, Chemical formula 6)

Embedded image

Embedded image

Embedded image [In the general formulas 4, 5 and 6, R ¹ , R ² ,
R ³ , R ⁴ and * have the same meanings as described above. ] In the dipeptide compound represented by the general formula of 3 used for the catalyst of the present invention, an isopropyl group as R ^1, an isobutyl group, sec- butyl group, tert- butyl group, a methyl group or a benzyl group Preferably, R ² Is preferably a benzyl group, an indol-3-ylmethyl group, an isopropyl group or an isobutyl group, R ³ is preferably a lower alkoxy group, and R ⁴ is preferably a hydrogen atom,
Preferably, at least two of R ⁵ , R ⁶ , R ⁷ and R ⁸ are hydrogen atoms.

The dipeptide compound represented by the general formula 3 used in the catalyst of the present invention is, for example, a compound represented by the formula 1

(Equation 1) (Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ ,
R ⁸ and * have the same meaning as described above. )
It can be produced by condensing a salicylaldehyde derivative such as 2-hydroxy-1-naphthaldehyde with a dipeptide.

[0005] The dipeptide used in the above formula for condensation with a salicylaldehyde derivative such as 2-hydroxy-1-naphthaldehyde can be produced according to a usual peptide synthesis technique.

For example, N-benzyloxycarbonyl-
S-valine, N-benzyloxycarbonyl-S-leucine, N-benzyloxycarbonyl-S-isoleucine, N-benzyloxycarbonyl-S-tert-leucine, N-benzyloxycarbonyl-S-alanine, N
-Benzyloxycarbonyl-S-phenylalanine or their corresponding R isomers and S-phenylalanine alkyl esters or amides (e.g. methyl or ethyl esters, lower alkyl esters having 1 to 4 carbon atoms such as mono- or di-, such as butylamide, diethylamide, etc.) Lower alkylamide) or S-tryptophan alkyl ester or amide or their R isomers are condensed by the mixed acid anhydride method in the presence of isobutyl chloroformate to give N-benzyloxycarbonyl-S-
After obtaining the corresponding dipeptide derivative such as valyl-S-phenylalanine methyl ester, and then performing a hydrogenolysis reaction in the presence of palladium-carbon,
It can be produced by condensing with a salicylaldehyde derivative such as 2-hydroxy-1-naphthaldehyde.

The titanium (IV) alkoxide used as a catalyst component is usually titanium (IV) tetraethoxide, titanium (IV) tetraisopropoxide, titanium (IV) tetrapropoxide, titanium (IV) tetrabutoxide. Lower alkoxides of titanium (IV) (e.g.,
C _1-4 alkoxides such as ethoxide, isopropoxide, propoxide and butoxide) are used, and the amount of the compound represented by the general formula (3) and the amount of the titanium (IV) alkoxide are generally about 1: 0 in molar ratio. 0.5 to 1: 2, preferably 1: 1 to 1: 2. In the catalyst of the present invention, it is presumed that the dipeptide compound represented by the general formula (3) and a titanium (IV) alkoxide form a complex, although it is not necessarily clear.

As a catalyst of the present invention, for example, Nap-S-Val-S-Phe-OMe as a dipeptide compound (R ¹ is an isopropyl group, R ² is a benzyl group, R ³
Is a methoxy group, R ⁴ is a hydrogen atom and the configuration is both S-form) and titanium (IV) tetraethoxide. When (R) -mandero is present in the reaction between benzaldehyde and hydrogen cyanide, Nitrile is formed and Na
pR-Val-R-Phe-OMe (in the compound represented by the formula 4, R ¹ is an isopropyl group, R ² is a benzyl group, R ³ is a methoxy group, R
^{When 4} is a hydrogen atom and the configuration is both R-forms) and titanium (IV) tetraethoxide is used, (S) -mandelonitrile is produced, and the catalyst of the present invention is a medicinal and agricultural chemical (for example, It is extremely useful as a catalyst for producing various optically active cyanohydrins which are useful as intermediates for producing pyrethroid insecticides), perfumes and the like.

In the catalyst of the present invention, as the dipeptide compound represented by the general formula 3, from the viewpoint of asymmetric yield, the amino acid components having the same configuration, that is, the steric configuration relating to the carbon atom indicated by * is either S or both R or R. It is preferable to use

[0010] In addition to the above-mentioned benzaldehyde, p-methylbenzaldehyde and one or two halogen atoms (for example,
M-methoxybenzaldehyde, naphthaldehyde, m-phenoxybenzaldehyde, aromatic aldehydes such as furfural, aliphatic aldehydes such as heptanal, and alicyclic rings such as cyclohexanecarbaldehyde which may be substituted with a fluorine atom, a chlorine atom, or a bromine atom. Formula aldehydes are included.

When the catalyst of the present invention is used in an asymmetric cyanohydrin synthesis reaction, the use amount thereof is 1 to 15 mol% based on the aldehyde compound, and the purpose can be sufficiently achieved.
In addition, the reaction is usually carried out by adding 1 to 5 moles of hydrogen cyanide to an aldehyde compound in an inert solvent such as toluene, methylene chloride, ethyl ether or isopropyl ether.
The reaction is carried out at 80 ° C. to room temperature, preferably at -50 ° C. to room temperature. After completion of the reaction, the reaction solution is poured into a dilute hydrochloric acid-methanol solution, and then excess hydrogen cyanide is removed under reduced pressure, followed by ordinary post-treatment to obtain the desired asymmetric cyanohydrin.

[0012]

Next, the present invention will be described in more detail with reference to Examples.
I do. Example 1 At room temperature under an argon atmosphere, Nap-S-Val-S-Trp-OMe (Chemical Formula 4)
In the compound shown, R ¹Is an isopropyl group, R^TwoIs in
Dol-3-ylmethyl group, R^ThreeIs a methoxy group, R^FourBut
Hydrogen atom, both in S configuration) 0.05 mmol
Suspended in 3 ml of ene, and mixed with titanium (IV) tetraethoxy.
0.05 mmol of sid was added. After stirring for 30 minutes, the reaction mixture
The solution was cooled to -78 ° C and 0.5 mmol of benzaldehyde was added.
0.75 mmol of hydrogen anion were added. Stir at -40 ° C for 3 hours
And then pour the reaction solution into dilute hydrochloric acid-methanol solution.
After removing excess hydrogen cyanide under reduced pressure.
Mandelonitrile was obtained from the organic layer in a yield of 85%. R
The ratio of body to S form was 94: 6.

[0013] The yield has been calculated from the integrated intensity of ¹ H-NMR spectrum of the crude product, the ratio of R and S-isomers, diastereomers of the product corresponding menthyl carbonate according to a conventional method After conversion into a stereomer pair, ¹ H-NMR
It is obtained from the integrated intensity of the signal corresponding to methine hydrogen in the spectrum. (Tanaka et al., J. Org. Chem., 5
5,181 (1990); Mori et al., Chem. Lett., 1989, 2119)

Example 2 Example 1 was repeated except that titanium (IV) tetraethoxide 0.05
Titanium (IV) tetraisopropoxide 0.05 instead of mmol
Instead of using 3 mmol and stirring at -40 ° C for 3 hours,
The same operation as in Example 1 was carried out except that stirring was continued at -20 ° C for 2.5 hours, whereby mandelonitrile was obtained in a yield of 96%. The ratio between the R-form and the S-form was 89:11.

Example 3 In Example 1, Nap-S-Val-S-Trp-OMe was used instead of Nap-S-Val-S-Trp-OMe.
Using S-Val-S-Phe-OMe, the same operation as in Example 1 was performed, except that stirring was continued at -40 ° C for 4 hours instead of stirring at -40 ° C for 3 hours, and mandelonitrile was removed. Obtained in 85% yield. The ratio between the R-form and the S-form was 93: 7.

Example 4 In Example 3, Nap-S-Val-S-Phe-OMe was used instead of Nap-S-Val-S-Phe-OMe.
The same operation as in Example 3 was performed except that R-Val-R-Phe-OMe was used, and mandelonitrile was obtained at a yield of 85%. The ratio between the R-form and the S-form was 9:91.

Example 5 In Example 2, Nap-S-Val-S-Trp-OMe was used instead of Nap-S-Val-S-Trp-OMe.
Using R-Val-S-Phe-OMe, the same operation as in Example 2 was carried out except that stirring was continued at -20 ° C for 4 hours instead of stirring at -20 ° C for 2.5 hours. 84% nitrile
In a yield of The ratio between the R-form and the S-form was 31:69.

Example 6 The procedure of Example 1 was repeated, except that 2-naphthaldehyde was used instead of benzaldehyde, and stirring was continued at -40 ° C. for 7.5 hours instead of stirring at -40 ° C. for 3 hours. By performing the same operation as in Example 1, α-hydroxy- (2-naphthyl) acetonitrile was obtained with a yield of 88%. The ratio of R-form to S-form was 95: 5.

Example 7 The same operation as in Example 6 was carried out except that furfural was used instead of 2-naphthaldehyde.
α-Hydroxyfurfurylnitrile was obtained in a yield of 74%. The ratio between the R-form and the S-form was 7:93.

Example 8 In Example 1, Nap-S-Val-S-Trp-OMe was used instead of Nap-S-Val-S-Trp-OMe.
S-Leu-S-Phe-OMe (a compound represented by Chemical Formula 4, wherein R ¹ is an isobutyl group, R ² is a benzyl group, R ³ is a methoxy group, R ⁴
Is a hydrogen atom and the configuration is both S-form), and -4
The same operation as in Example 1 was carried out except that stirring was continued at -20 ° C for 4 hours instead of stirring at 0 ° C for 3 hours, thereby obtaining mandelonitrile in a yield of 93%. The ratio of R-form to S-form was 87.5: 12.5.

Example 9 Example 1 was repeated except that stirring was continued at -20 ° C. for 2.5 hours instead of stirring at −40 ° C. for 3 hours.
The same operation as described above was performed to obtain mandelonitrile in a yield of 97%. The ratio of R-form to S-form was 91: 9.

Example 10 The procedure of Example 3 was repeated, except that stirring was continued at -20 ° C. for 4 hours instead of stirring at −40 ° C. for 4 hours. % Yield. The ratio of R-form to S-form was 91: 9.

Example 11 In Example 2, Nap-S-Val-S-Trp-OMe was used instead of Nap-S-Val-S-Trp-OMe.
S-Ile-S-Phe-OMe (a compound represented by the chemical formula 4, wherein R ¹ is
a c-butyl group, R ² is a benzyl group, R ³ is a methoxy group,
Mandelonitrile was obtained in a yield of 94% by performing the same operation as in Example 2 except that R ⁴ was a hydrogen atom and the configuration was both S-forms. The ratio of R-form to S-form is 86.5: 13.5
Met.

Example 12 In Example 2, Nap-S-Val-S-Trp-OMe was replaced with Nap-S-Val-S-Trp-OMe.
St-Leu-S-Phe-OMe (R ¹ is te
rt-butyl group, R ² is a benzyl group, R ³ is a methoxy group, R ⁴ is a hydrogen atom and the configuration is both S), methylene chloride is used as a solvent instead of toluene at -20 ° C. -20 ° C instead of 2.5 hours stirring
The operation was carried out in the same manner as in Example 2 except that stirring was continued for 4.5 hours to obtain mandelonitrile in a yield of 74%. The ratio between the R-form and the S-form was 90:10.

Example 13 In Example 2, Nap-S-Val-S-Trp-OMe was replaced with Nap-S-Val-S-Trp-OMe.
S-Ala-S-Phe-OMe (a compound represented by Chemical Formula 4 wherein R ¹ is a methyl group, R ² is a benzyl group, R ³ is a methoxy group, R ⁴ is a hydrogen atom and the configuration is both S-forms) -20 ° C)
The operation was carried out in the same manner as in Example 2 except that stirring was continued at -20 ° C for 4 hours instead of 2.5 hours to obtain mandelonitrile in a yield of 80%. R to S ratio is 7
9.5: 20.5.

Example 14 In Example 2, Nap-S-Val-S-Trp-OMe was replaced with Nap-S-Val-S-Trp-OMe.
S-Phe-S-Phe-OMe (a compound represented by Chemical Formula 4 in which R ¹ is a benzyl group, R ² is a benzyl group, R ³ is a methoxy group, R ⁴ is a hydrogen atom and the configuration is both S-forms) ) And -20
The same operation as in Example 2 was carried out except that stirring was continued at -20 ° C for 7.5 hours instead of stirring at 2.5 ° C for 2.5 hours, thereby obtaining mandelonitrile in a yield of 94%. The ratio between the R-form and the S-form was 83.5: 16.5.

Example 15 In Example 2, Nap-S-Val-S-Trp-OMe was replaced with Nap-S-Val-S-Trp-OMe.
S-Val-S-Phe-NEt2 (a compound represented by Chemical Formula 4 wherein R ¹ is an isopropyl group, R ² is a benzyl group, R ³ is a diethylamino group, R ⁴ is a hydrogen atom, and the configuration is both S-forms) ) And stirring at −20 ° C. for 2.5 hours instead of −4
The same operation as in Example 2 was carried out except that stirring was continued at 0 ° C. for 3 hours and further at −20 ° C. for 15 hours, thereby obtaining mandelonitrile in a yield of 88%. The ratio between the R-form and the S-form was 90:10.

Example 16 In Example 4, m-phenoxybenzaldehyde was used instead of benzaldehyde. Instead of continuing stirring at -40 ° C. for 4 hours, -20 ° C. was further added at -40 ° C. for 11 hours.
The operation was performed in the same manner as in Example 4 except that stirring was continued for 12 hours to obtain α-hydroxy-m-phenoxyphenylacetonitrile in a yield of 85%. The ratio between the R-form and the S-form was 7:93.

Example 17 Example 3 was repeated except that cyclohexanecarbaldehyde was used instead of benzaldehyde, and stirring was continued at -40 ° C for 1.5 hours instead of stirring at -40 ° C for 4 hours. The same operation as described above was performed to obtain α-hydroxy-cyclohexylacetonitrile with a yield of 99%. R
The ratio of body to S body was 77:23. In this example, the ratio of the R-form to the S-form was derived to the corresponding diastereomer pair of (+)-1-methoxy-1-phenyl-2,2,2, -trifluoro-propionate. rear,
It is determined from the isomer ratio by gas chromatography.

Example 18 The procedure of Example 2 was repeated, except that heptanal was used instead of benzaldehyde, and stirring was continued at -40 ° C. for 1 hour instead of stirring at -20 ° C. for 2.5 hours. To obtain 2-hydroxyoctanenitrile in 9
Obtained in 9% yield. The ratio between the R-form and the S-form was 67:33. In this example, the ratio of the R-form to the S-form was determined by the corresponding (+)-1-methoxy-1-phenyl-2,2,2.
It is determined from the isomer ratio by gas chromatography after leading to a diastereomeric pair of 2, -trifluoro-propionic acid ester.

Example 19 In Example 2, Nap-S-Val-S-Trp-OMe was used instead of Nap-S-Val-S-Trp-OMe.
S-Val-S-Phe-OH (a compound represented by Chemical formula 4, wherein R ¹ is an isopropyl group, R ² is a benzyl group, R ³ is a hydroxy group,
R ⁴ is a hydrogen atom and the configuration is both S-forms)
Instead of stirring at −20 ° C. for 2.5 hours, the same operation as in Example 2 was carried out except that stirring was continued at −20 ° C. for 3 hours and further at 0 ° C. for 16 hours to obtain a 93% yield of mandelonitrile. Rate obtained. The ratio between the R-form and the S-form was 71:29.

Example 20 In Example 2, Nap-S-Val-S-Trp-OMe was used instead of Nap-S-Val-S-Trp-OMe.
S-PhGly-S-Phe-OMe (a compound represented by Chemical Formula 4, wherein R ¹ is a phenyl group, R ² is a benzyl group, R ³ is a methoxy group, R
⁴ is a hydrogen atom and the configuration is both S)
Instead of continuing to stir at 20 ° C for 2.5 hours,
The same operation as in Example 2 was performed except that the stirring was continued for 0 hour, to obtain mandelonitrile in a yield of 62%. R body and S
The ratio with the body was 62.5: 37.5.

Example 21 In Example 2, Nap-S-Val-S-Trp-OMe was replaced with Nap-S-Val-S-Trp-OMe.
S-Val-S-PhGly-OMe (a compound represented by Chemical Formula 4 wherein R ¹ is an isopropyl group, R ² is a phenyl group, R ³ is a methoxy group, R ⁴ is a hydrogen atom and the configuration is both S-forms) ) Instead of continuing stirring at -20 ° C for 2.5 hours,
The same operation as in Example 2 was carried out except that stirring was continued at 4 ° C. for 4 hours, to obtain mandelonitrile in a yield of 86%. The ratio between the R-form and the S-form was 62:38.

Example 22 In Example 2, Nap-S was replaced with Nap-S-Val-S-Trp-OMe.
-Val-S-Pro-OEt (a compound represented by Chemical Formula 4, wherein R ¹ is an isopropyl group, R ² and R ⁴ are trimethylene groups, R ³ is an ethoxy group and the configuration is both S-forms), -20 ° C
The procedure of Example 2 was repeated, except that stirring was continued at -20 ° C for 20 hours, instead of 2.5 hours, to obtain mandelonitrile in a yield of 74%. The ratio between the R-form and the S-form was 66.5: 33.5.

Example 23 Example 1 was repeated, except that stirring was continued at -60 ° C for 16 hours instead of stirring at -40 ° C for 3 hours.
The same operation as described above was performed to obtain mandelonitrile in a yield of 83%. The ratio of R-form to S-form was 95: 5.

Example 24 In Example 3, titanium (IV) tetraethoxide (0.0%
5 mol) in place of titanium (IV) tetrabutoxide (0.05
Mol), and the same operation as in Example 3 was carried out, except that stirring was continued at -20 ° C for 4 hours instead of stirring at -40 ° C for 4 hours, to obtain mandelonitrile in a yield of 84%. Was. The ratio of R-form to S-form was 89:11.

Example 25 In Example 1, Nap-S-Val-S-Trp-OMe was replaced with Nap-S-Val-S-Trp-OMe.
Using S-Ile-S-Phe-OMe, the same operation as in Example 1 was carried out except that stirring was continued at -40 ° C for 4 hours instead of stirring at -40 ° C for 3 hours, and mandelonitrile was added to 85%. % Yield. The ratio of R-form to S-form was 87.5: 12.5.

Example 26 In Example 1, Nap-S-Val-S-Trp-OMe was used instead of Nap-S-Val-S-Trp-OMe.
S-Val-S-Val-OMe (compound represented by Chemical Formula 4, wherein R ¹ is an isopropyl group, R ² is an isopropyl group, R ³ is a methoxy group, R ⁴ is a hydrogen atom, and the configuration is S) Instead of stirring at −40 ° C. for 3 hours, use −40 ° C.
The operation was performed in the same manner as in Example 1 except that stirring was continued for 4 hours to obtain mandelonitrile in a yield of 64%. R body and S
The body ratio was 93.5: 6.5.

Example 27 In Example 1, Nap-S-Val-S-Trp-OMe was replaced with Nap-S-Val-S-Trp-OMe.
S-Val-S-Leu-OMe (a compound represented by Chemical Formula 4, wherein R ¹ is an isopropyl group, R ² is an isobutyl group, R ³ is a methoxy group,
R ⁴ is a hydrogen atom and the configuration is both S)
The same operation as in Example 1 was carried out except that stirring was continued at -40 ° C for 4 hours instead of stirring at 40 ° C for 3 hours, thereby obtaining mandelonitrile in a yield of 72%. The ratio of R-form to S-form was 79.5: 20.5.

Example 28 Example 1 was repeated except that m-methoxybenzaldehyde was used instead of benzaldehyde and stirring was continued at -40 ° C for 4 hours instead of stirring at -40 ° C for 3 hours. By performing the same operation, α-hydroxy- (m-
(Methoxyphenyl) -acetonitrile was obtained in 80% yield. The ratio of R-form to S-form was 92.5: 7.5.

Example 29 In Example 1, Sal- was replaced by Nap-S-Val-S-Trp-OMe.
S-Val-S-Trp-OMe (a compound represented by Chemical Formula 5, wherein R ¹ is an isopropyl group, R ² is an indol-3-ylmethyl group, R
³ was a methoxy group, R ⁴ was a hydrogen atom, and the configuration was S). Instead of stirring at −40 ° C. for 3 hours, stirring was continued at −40 ° C. for 4 hours. The same operation was performed to obtain mandelonitrile in a yield of 83%. The ratio of R-form to S-form was 89.5: 10.5.

Example 30 In Example 1, Nap was replaced with Nap-S-Val-S-Trp-OMe.
^1- S-Val-S-Trp-OMe (a compound represented by Chemical Formula 6, wherein R ¹ is an isopropyl group, R ² is an indol-3-ylmethyl group, R ³ is a methoxy group, R ⁴ is a hydrogen atom, Example 1 except that stirring was continued at −40 ° C. for 4 hours instead of stirring at −40 ° C. for 2 hours.
The same operation as described above was performed to obtain mandelonitrile in a yield of 57%. The ratio of R-form to S-form was 87.5: 12.5.

Example 31 In Example 1, Sal was replaced with Nap-S-Val-S-Trp-OMe.
^1- S-Val-S-Phe-OMe (a compound represented by Chemical Formula 3, wherein R ¹ is an isopropyl group, R ² is a benzyl group, R ³ is a methoxy group, R ⁴ is a hydrogen atom, R ⁵ , R ⁶ and R ⁷ is a hydrogen atom, R ⁸ is a methoxy group, and the configuration is S). Instead of stirring at −40 ° C. for 3 hours, −40 ° C.
The operation was carried out in the same manner as in Example 1 except that stirring was continued for 2 hours to obtain mandelonitrile in a yield of 68%. R body and S
The body ratio was 74:26.

Example 32 In Example 1, Sal was replaced with Nap-S-Val-S-Trp-OMe.
^Two-S-Val-S-Phe-OMe (a compound represented by the formula¹But
Isopropyl group, R^TwoIs indol-3-ylmethyl
Group, R^ThreeIs a methoxy group, R^FourIs a hydrogen atom, R^FiveAnd R
⁷Is a hydrogen atom, R ⁶And R⁸Is a tert-butyl group, steric
And stirring at −40 ° C. for 3 hours.
Instead of continuing, stirring was continued at -20 ° C for 2.5 hours.
Performs the same operation as in Example 1 and converts mandelonitrile to 7
Obtained in 0% yield. The ratio of R-form to S-form is 70:30
Was.

[0045]

The asymmetric induction catalyst of the present invention is a useful catalyst which gives high yield and high optical purity in the production of cyanohydrin by adding hydrogen cyanide to an aldehyde compound.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI C07C 255/37 C07C 255/37 C07D 317/64 C07D 317/64 // C07B 61/00 300 C07B 61/00 300

Claims (15)

(57) [Claims] 1. A compound represented by the general formula: (Wherein, R ¹ is an isopropyl group, an isobutyl group,
- butyl group, tert- butyl group, a methyl group, a phenyl group or <br/> other represents a benzyl group, R ² represents benzyl or indol-3-ylmethyl group, an isopropyl group, an isobutyl group or a phenyl group, R ³ represents a lower alkoxy group, a hydroxy group or a mono- or di-lower alkylamino group, R ⁴ represents a hydrogen atom, or R ² and R ⁴ are bonded at a terminal to form a trimethylene group.
R ⁵ , R ⁶ , R ⁷ and R ⁸ are the same or different and represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group, or R ⁵ and R ⁶ , R ⁶ and R ⁷ , or R ⁷ And R ⁸ are bonded at the terminal to represent a group represented by CH ＝ CH—CH ＝ CH or a group represented by OCH ₂ O. * Indicates the configuration of S or R. Asymmetric induction catalyst comprising a dipeptide compound represented by the formula (I) and a titanium (IV) alkoxide 2. A compound represented by the general formula: (Wherein R ¹ , R ² , R ³ , R ⁴ and * have the same meanings as in claim 1) and a titanium (IV) alkoxide. 3. A method for producing an optically active cyanohydrin according to claim 1.
Or the asymmetric induction catalyst according to 2 4. The asymmetric induction catalyst according to claim 1, 2 or 3 for producing optically active cyanohydrin by adding hydrogen cyanide to an aldehyde compound. 5. The catalyst according to claim 4, wherein the aldehyde compound is an aromatic aldehyde. 6. The catalyst according to claim 4, wherein the aldehyde compound is benzaldehyde. 7. The asymmetric induction catalyst according to claim 4, wherein the aldehyde compound is m-phenoxybenzaldehyde which may be substituted with one or two halogen atoms. 8. The method according to claim 1, wherein the two configurations are S.
Asymmetric induction catalyst according to 2, 3, 4, 5, 6, or 7 9. The method of claim 1, wherein the two configurations are both R.
Asymmetric induction catalyst according to 2, 3, 4, 5, 6, or 7 10. A method using the catalyst according to claim 1 or 2 in the production of cyanohydrin by adding hydrogen cyanide to an aldehyde compound. 11. The method according to claim 10, wherein the aldehyde compound is an aromatic aldehyde. 12. The method according to claim 10, wherein the aldehyde compound is benzaldehyde. 13. The method according to claim 10, wherein the aldehyde compound is m-phenoxybenzaldehyde which may be substituted with one or two halogen atoms. 14. The method according to claim 1, wherein the two configurations are S.
14. A catalyst according to claim 10, 11, 12 or 13.
How to describe 15. The method of claim 1, wherein the two configurations are both R.
14. A catalyst according to claim 10, 11, 12 or 13.
How to describe