JPH0314534A - Production of beta-hydroxycarboxylic acid derivative - Google Patents

Abstract

PURPOSE:To permit safe and advantageous production of the subject compound which is used as a synthetic intermediate of medicines and agrochemicals by using a specific cobalt complex as a catalyst to allow readily available alpha,beta-unsaturated carboxylic acid to react with a carbonyl compound and a phenylsilane. CONSTITUTION:A cobalt complex of a beta-dicarbonyl compound of formula I (R<1>, R<2>, R<4> and R<5> are independent to one another and 1 to 10C lower alkyl, cycloalkyl, aryl; R<3>, R<6> are independent mutually and lower alkyl, aryl, arylalkyl) is used as a catalyst to effect reaction between an alpha,beta-unsaturated carboxylic acid derivative of formula II (R<7>, R<8>, R<9> are independent to one another and lower alkyl of 1 to 10 carbon atoms; X is H, lower alkoxy of 1 to 10 carbon atoms, phenoxy), a carbonyl compound of formula III (R<10>, R<11> are H, alkyl of 1 to 20 carbon atom) and phenylsilane. After reaction, phenylsilane is preferably eliminated by hydrolysis or solvolysis to give the compound of formula IV.

Description

[Detailed description of the invention] Next, the present invention will be specifically explained.

The present inventor investigated the reaction between an α,β-unsaturated carboxylic acid derivative and a carbonyl compound using various catalysts, and discovered a completely new reaction, leading to the present invention.

First, the cobalt complex used as a catalyst in the production method of the present invention will be explained.

The cobalt complex used in the present invention is a cobalt complex of a β-dicarbonyl compound, and this cobalt complex can be represented by the following formula [1].

... [1] l In the above formula [I], R, R2 R' and R5 are
3 atoms or groups each independently selected from the group consisting of a hydrogen atom, a lower alkyl group having 1 to 10 carbon atoms, a cycloalkyl group, an aryl group, an arylalkyl group, a trifluoromethyl group, an alkoxycarbonyl group, and a carbamoyl group. R and R6 each independently have a carbon number of 1
Represents a group selected from the group consisting of ~10 lower alkyl groups, aryl groups, arylalkyl groups, and cycloalkyl groups.

The above-mentioned lower alkyl group is an alkyl group having 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms, and this alkyl group may be linear or branched. Specific examples of such alkyl groups include methyl group, ethyl group, n-
Probyl group, isobrobyl group, butyl group, tec-
butyl group, t-butyl group, isobutyl group, monopentyl group, 1-hexyl group, l-heptyl group, octyl group,
Mention may be made of the isooctyl group and the monononyl group. Among these lower alkyl groups, R SR2, R'
Preferred alkyl groups as R3 and R5l are alkyl groups having 1 to 6 carbon atoms, particularly ethyl, n-butyl, tobutyl, isobutyl, and n-hexyl groups, and preferred alkyl groups as R3 and R6 have a carbon number of 1 to 6 alkyl groups, especially ethyl, toptyl, t-butyl, isobutyl, n-hexyl.

Further, specific examples of the cycloalkyl group include a cyclohexyl group, a cyclobentyl group, a cycloheptyl group, and a cyclooctyl group. In addition, as mentioned above, the cycloalkyl group may have a substituent on the cycloalkyl group.

12 Among these cycloalkyl groups, RR, R and R
Preferred cycloalkyl groups 4 as 5 are 1-methylcyclobentyl group, 1-methylcyclohexyl group, 4-tobutylcyclohexyl group, and R1
Preferred cycloalkyl groups as R6 are 1-methylcyclopentyl group and 1-methylcyclohexyl group.

In the above aryl group, the hydrogen atom on the aromatic ring may be substituted with another atom such as a halogen atom, or a substituent, etc. Specific examples of such an aryl group include:
In addition to halogenated phenyl groups such as p-promophenyl groups, naphthyl groups, and phenyl groups, the following formulas (1) to (
14) Furthermore, as the arylalkyl group,
In the following formula, however, in the above formula, R represents a hydrogen atom or an alkyl group, m is an integer of 0 to 3, preferably 0 to 1, and n is an integer of 1 to 4, preferably 1 to 3. . Further, the hydrogen atom on the aromatic ring in the above formula may be substituted with another atom such as a halogen atom, or a substituent.

Specific examples of these groups include the following formula (1
Examples include groups represented by 5) to (33).

CH30+CH2-...(15) and R5
Preferred arylalkyl groups include formula (23), (
24), (25), (26), (27), (28), (
29), (30), (31), (32) and (33)
It is a group represented by

Furthermore, examples of the alkoxycarbonyl group include groups represented by the following formula.

O However, in the above formula, p represents an integer of 1 to 6. Specific examples of such an alkoxycarbonyl group include a methoxy group, an ethoxy group, an n-propoxy group, and an alkoxycarbonyl group in which the alkoxy group is an n-ptoxy group or an n-pentoxy group. Among these alkoxy carbonyl groups, preferable groups as R 2 , R 2 , R 2 and R 5 are alkoxycarbonyl groups in which the alkoxy group is a methoxy group, an ethoxy group, a broboxy group or a butoxy group.

Further, the carbamoyl group can be represented by the following formula.

However, in the above formula, R and R15 each independently represent an atom selected from a hydrogen atom, a lower alkyl group, and a cycloalkyl group, or 14 represents a group. Furthermore, R and Rl5 may jointly form a ring, in which case -0-16- -s-, -NR (however, RI6 is a lower alkyl group or a hydrogen atom), or -N R and Rl5 may be connected via = to form a ring.

Here, examples of the lower alkyl group and the cycloalkyl group include the groups exemplified above.

Specific examples of such carbamoyl groups include dimethylaminocarbamoyl group, methylaminocarpamoyl group, diethylaminocarbamoyl group, dipropylaminocarbamoyl group, methylethylaminocarbamoyl group,
Examples include a piperidinocarbamoyl group, a piperazinocarbamoyl group, a morpholinocarbamoyl group, an ethylaminocarbamoyl group, a cyclohexylaminocarbamoyl group, and a cyclohexylethylaminocarbamoyl group.

Among these carbamoyl groups, R in formula [I]
, R , R and R5 are preferred 1
The 2 4 group is a diethylaminocarbamoyl group, a piverizinocarbamoyl group, a biperazinocarbamoyl group, and a morpholinocarbamoyl group.

! R SR2, R4 and R5 in these formula [I] may be the same or different.

Furthermore, R3 and R6 may be the same or different.

In the present invention, among the cobalt complexes represented by the above formula [I], compounds having particularly excellent catalytic activity are compounds represented by the following formulas [I-11 and [I-2].

R18 and Rl9 each independently represent a lower alkyl group such as a methyl group, a rhoprobyl group, a C-butyl group, a tobutyl group, or an n-pentyl group; a substituted or unsubstituted aryl group such as a phenyl group or a methoxyphenyl group; A group; a cycloalkyl group such as a cyclohexyl group; a hydrogen atom; any one of the following groups or atoms is preferable.

...[I-11 16 17 However, in the above formula [I-11, R, R...
・[I-2] 24 26 However, in the above formula [I'-2], RR27
26' R and R are each independently preferably a lower alkyl group such as a methyl group, an ethyl group, a Set-butyl group, or a (monobutyl group), 25 Furthermore, R and R2 are each independently a methoxy group, Lower alkoxy groups such as ethoxy group, Sec-butyl group and 1-butyl group; Lower alkyl groups such as methyl group and ethyl group are preferred.

Among the compounds represented by the above formula [I], particularly preferred compounds as the catalyst used in the present invention are compounds represented by the following formulas (50) to (94).

(50) Bis(3,7-dimethyl-4,6-nonanedionato)cobalt(n) (50-1) Bis(2,2,6,6-tetramethyl-3,5-heptodionato)cobalt(II) (50-
2) Bis(2.6-dimethyl-3.5-heptodionato)cobalt(II) ... (5 0) ... (50-2) (5 1) Bis(1 3-dicyclohexyl 1 3 (5 3) Bis(2 4-hexanedionate) Covabrobandionato) Cobalt(II) Ruth(n) (5 2) Bis(2 2 8.8-tetramethyl-4,6- (5 4) Bis[1 .3-Bis(4-methoxyphenynonanedionate) Cobalt(II) = 1 3-propanedionato] Cobalt(If) (5 5) Bis(4 4-dimethyl-l-phenyl(5 7) Bis(2 2-dimethyl-3 5-hexanedi-1 3-pentanedionato) Cobalt (It) Onato) Cobalt (n) ... (5 5) (56) Bis(2 4-nonanedionato) Cobalt (n) (5 8 ) Bis[4,6-nonanedionato) Cobalt(II) ... (5 6) ... (5 8) (5 9) Bis(l-phenyl-1,3-butanedio(6 1) Bis(i- Ethoxycarbonyl-13-nato) Cobalt(n) Butanedionato) Cobalt(II) O... (6 1) (62) Bis(1-+-ptoxycarbonyl-4.4(60) Bis(acetyl) acetonato) cobaldimethyl-1,3-pentanedionato) cobalt(n) (n) ... (60) 0 ... (62) (6 3) bis(l-methoxycarbonyl-1.3- ( 6 5) Bis(!-ethoxycarbonyl-4-4-butanedionato) Cobalt(II) Dimethyl-1,3-pentanedionato) Cobalt(II) O... (6 5) (6 6) Bis(lm- Proboxycarbonyl-4. 4-dimethyl-1,3-pentanedionato) cobalt (64) bis(1-methoxycarbonyl-4.4-to(n) dimethyl-1 3-pentanedionato) cobalt (n) O ... (66) 0 ... (6 4) (67) Bis(2-acetyl-1-phenyl-1,3
-pentanedionato) cobalt (n) (69) bis(2-ethoxycarbonyl-1.3-
butanedionato)cobalt(II) (68) bis(2-methoxycarbonyl-1,3-butanedionato)cobalt(n) (70) bis(j-set-butoxycarbonyl-1
．． 3-butanedionato)cobalt(n)(71) can be obtained by adding a cobalt compound such as cobalt bis(2-t-ptoxycarbonyl-1.3).

... (7 1) Note that such a cobalt complex of a β-dicarbonyl compound may be a hydrate or a salt.

In the present invention, the expression "cobalt complex of a β-dicarbonyl compound" also includes hydrates and salts of cobalt complexes of a β-dicarbonyl compound.

The cobalt complex of a β-dicarbonyl compound as described above can be prepared, for example, in an alcoholic or aqueous solution in which a dicarbonyl compound or a salt thereof corresponding to the ligand of the complex to be obtained is dispersed or dissolved, as shown below. , an aqueous sodium hydroxide solution is added dropwise to this solution with stirring, and then the reaction between the salt β-dicarbonyl compound and the cobalt compound is carried out by adjusting the pH value of the reaction solution to be alkaline within the range of 8 to 12. It will be done as follows. This reaction is usually O
At a reaction temperature of ~50°C, it is completed in 0.1-2 hours.

The cobalt complex produced as described above usually has 1 4 2 cobalt atoms in the above formula [I].
This is a compound in which R 1 and R 2 , R 1 and R 1 , and R3 and R6 are the same group with 5 as the point of symmetry.

The cobalt complex of the present invention may be a compound that has symmetry as described above, but it does not need to have symmetry, and compounds that do not have such symmetry may be It can be produced by preparing two or more types of cobalt complexes having the same properties, mixing the two or more types of cobalt complexes, and refluxing the mixture in the presence of a reaction solvent such as toluene. Examples of the above reactions are shown below.

As the β-dicarbonyl compound used in producing the cobalt complex as described above, any compound capable of forming the above cobalt complex can be used without particular limitation. Specific examples of such β-dicarbonyl compounds include 3,7-dimethyl-4,6-mononanthion, 1,3-dicyclohexyl-1,3-propanedione, 2,2.
8. 8-tetramethyl-4,6-nonanedione, 1.
3-butanedione, 1,3-bis(4-methoxyphenyl)-1,3-propanedione, 1-pentafluorophenyl-1,3-butanedione,
4,4-dimethyl-1-pentafluorophenyl-1.
3-pentanedione, 4.4-dimethyl-1-phenyl-1,3-pentanedione, 1-(4-promophenyl-4.4-dimethyl-13
-pentanedione, 2. 4-nonanedione, 2,2-dimethyl-3,5-hexanedione, 4.6-nonanedione, 1-ethoxycarbonyl-1,3-butanedione, 1-
Butoxycarbonyl-4,4-dimethyl-1,3-pentanedione, 1-methoxycarbonyl-4,4-dimethyl-1,3-
Putanedione! -methoxycarbonyl-1,3-butanedione, 1-
Methoxycarbonyl-4,4-dimethyl-1,3-pentanedione, 1-ethoxycarbonyl-4,4-dimethyl-1,3-
Pentanedione, 1-ropeboxycarbonyl-4,4-dimethyl-1
3-pentanedione, 2-ethoxycarbonyl-1-phenyl-1,3-butanedione, 3-ethoxycarbonyl-2,4-pentanedione, 2
-acetyl-1-phenyl-1,3-butanedione, 2
-Methoxymethyleneacetoacetic acid methyl ester, 2-ethoxymethyleneacetoacetic acid methyl ester, 2-methoxymethyleneacetoacetic acid Sec-butoxy ester 2-rohydroxymethyleneacetoacetic acid monot-butyl ester, 1,1.1-}refluoro-5 -(4-methylphenyl)-2,4-pentanedione, 1, I, I- trifluoro-5-(4-methoxyphenyl)-2,4-pentanedione, and 1-phenyl-1.3- Propanedione may be mentioned. These β-dicarbonyl compounds can be used alone or in combination.

There is no particular restriction on the cobalt compound used to produce the cobalt complex of the present invention together with the above β-dicarbonyl compound, but examples of the cobalt compound that can be used in the present invention include, for example, C e C I 2 Inorganic cobalt compounds such as CO (CH3
Examples include organic cobalt compounds such as C 0 0 ) 2, and these cobalt compounds can be used alone or in combination.

Although the reaction between the β-dicarbonyl compound and the cobalt compound can be carried out in water, it is preferable to carry out the reaction in a mixed solvent of water and alcohol. The weight ratio of water to alcohol in the reaction solvent used in the present invention is usually within the range of 10:90 to 100:0.

The α,β monounsaturated carboxylic acid derivative used in the present invention can be represented by the following formula [1].

0 78 However, in the above formula [■], R SR and R
9 each independently represents a hydrogen atom or a lower alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms, X is a hydrogen atom,
Lower alkoxyl group having 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms, phenoxy group having 1 to 10 carbon atoms, amino group, alkylamino group (wherein R and R13 are each independently 12 hydrogen atoms, 1 carbon number l) R1 represents an atom or group selected from the group consisting of a lower alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 aryl groups, and an aryl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms;
2 and Rl3 may be linked to each other to form a ring) and an arylalkyl group having 7 to 20 carbon atoms, preferably 7 to 10 carbon atoms.

Therefore, examples of α,β monounsaturated carboxylic acid derivatives used in the present invention include acrylic acid, methacrylic acid, crotonic acid, methyl acrylate, ethyl acrylate, phenyl acrylate, methyl methacrylate, and ethyl methacrylate. , phenyl methacrylate, methyl crotonate, ethyl crotonate, phenyl crotonate, acrylamide, acrylic acid methylamide, acrylic acid ethylamide, acrylic acid propylamide, acrylic acid dimethylamide, acrylic acid diethylamide, acrylic acid diisopropylamide, acrylic acid piperidinamide, Acrylic acid morpholinoamide, methacrylamide, methacrylic acid methylamide, methacrylic acid ethylamide, methacrylic acid propylamide, methacrylic acid dimethylamide, methacrylic acid diethylamide, methacrylic acid diisopropyramide, methacrylic acid piberidinoamide, methacrylic acid morpholinoamide, croton Examples include amide, crotonic acid methylamide, crotonic acid ethylamide, crotonic acid propylamide, crotonic acid dimethylamide, crotonic acid diethylamide, crotonic acid diisoprobylamide, crotonic acid piperidinamide, and crotonic acid morpholinoamide.

The carbonyl compound used in the present invention has the following formula [
III].

However, in the above formula [I1[], R11 and R1
2 each independently represents a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, an alkenyl group having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, and 1 to 20 carbon atoms;
It preferably represents one type of atom or group selected from the group consisting of 3 to 6 cycloalkyl groups, and R11 and R12
and have 2 to 10 carbon atoms, preferably 2 to 10 carbon atoms, connected to each other.
You may also use a ring of 6.

Thus, examples of such carbonyl compounds include formaldehyde, ethanal, probanal, pentanal, hexanal, octanal, decanal, undecanal, acrolein, 2-butenal, 2-hexenal, 4-hexanal, 2-octanal, 2
- aldehydes such as undecanal, benzaldehyde, cinnamaldehyde, furfural, cyclopropylene, cyclopentylcarbaldehyde, cyclohexylcarbaldehyde, 2-phenylethanal and 4-phenylbutanal; acetone, 2-bropanone, 2-phenylbutanal; -butanone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, 2-octanone, 2-decanone and 2-dodecanone; acetophenone, propiophenone, indanone and penzophenone; cyclopropanone, cycloptanone, cyclobentanone , cyclohexanone and cyclooctanone; Ketones such as methyl vinyl ketone, mesityl oxide, cyclopentenone, cyclohexenone, penzalacetone and chalcone may be mentioned. These compounds can be used alone or in combination.

The phenylsilane used in the present invention is C H
−SIH3.

65 The production of the β-hydroxycarboxylic acid derivative of the present invention using the catalyst and raw materials as described above is usually carried out under the following conditions.

In the present invention, the amount of cobalt complex as a catalyst is usually 0.00 mol per 1.0 mol of the carbonyl compound used.
It is used in amounts ranging from 1 to 1.0 mol, preferably from 0.005 to 0.2 mol. In addition, this cobalt complex is
It can be used alone or supported on a carrier.

By using a cobalt complex in the amounts mentioned above, β
-Hydroxycarboxylic acid derivatives can be efficiently produced.

In the present invention, the α,β-unsaturated carboxylic acid compound used as a raw material is usually 1.0 to 100 mol, preferably 1.05 mol, per 1 mol of the carbonyl compound used.
Use in amounts of ~5.0 moles.

In addition, phenylsilane is used as carbonyl compound 1
Usually 1.0 to 100 mol, preferably l
．． It is used in an amount of 0.05 to 5.0 mol.

The above reaction is usually carried out in an inert gas atmosphere. Examples of the inert gas that can be used in this case include nitrogen gas and argon gas. Further, this reaction can be carried out under any pressure condition, from reduced pressure to increased pressure.

In particular, in the present invention, nitrogen gas and/or argon gas is used as the inert gas, and the pressure is 0.1 to 50 atm.
It is preferable to carry out the reaction at a pressure of 0.5 to 5 atm.

Further, this reaction temperature can be appropriately set in consideration of other reaction conditions, but is usually set within the range of -80 to 200°C, preferably -30 to 100°C.

By reacting at such a temperature, usually 0.1
The reaction is completed in ~100 hours, preferably 0.5 to 20 hours.

Although the production method of the present invention does not particularly require the use of a reaction solvent, a reaction solvent can also be used.

In the present invention, when a reaction solvent is used, any solvent that can be used is not particularly limited as long as it does not have activity against the catalyst, reaction raw materials, and reaction products.

Examples of such reaction solvents include hydrocarbon solvents such as hexane, hebutane, octane, benzene, toluene and xylene; halogens such as dichloromethane, 1,2-dichloroethane, chloroform and chlorobenzene; methyl formate, formic acid Esters such as ethyl, ethyl acetate, methyl acetate and butyl acetate; ether solvents such as tetrahydrofuran, diethyl ether, dibutyl ether and dioxane can be mentioned. These solvents can be used alone or in combination.

Particularly preferred solvents are benzene, toluene, 1,2-
It is dichloroethane.

When carrying out the reaction using a solvent, the solvent is usually 5 to 100 parts by weight per 100 parts by weight of the carbonyl compound,
Preferably it is used in an amount of 10 to 50 parts by weight.

By carrying out the reaction in this manner, a β-hydroxycarboxylic acid derivative represented by the following formula [IV] can be obtained.

Furthermore, in addition to the compound represented by the above formula [IV], the following formula [
A compound represented by V] is also produced.

Wings However, in the above formula [V], n is an integer of 1, 2, or 3.

Moreover, the above formula [IV] and [. ■], R8~
RII has the same meaning as above.

In the present invention, by hydrolyzing or solvent decomposing the silyl ether represented by the above formula [V],
A β-hydroxycarboxylic acid derivative represented by [IV] can be obtained.

In this case, the water decomposition method may be performed by adding water to the reaction product and stirring, and the solvent decomposition method may be performed by adding alcohols such as methanol, ethanol, or water or stirring after the reaction is completed.

Furthermore, during hydrolysis or solvent decomposition, an acid catalyst such as hydrochloric acid or an alkali catalyst such as potassium hydroxide can be added as necessary.

The β-hydroxycarboxylic acid derivative represented by [IV] thus produced can be extracted, recrystallized, sublimated, distilled,
It can be separated and purified by commonly used separation operations such as chromatography.

Effects of the Invention The present invention provides a novel method for producing β-hydroxycarboxylic acid derivatives.

According to the method for producing β-hydroxycarboxylic acid derivatives according to the present invention, since a cobalt complex is used as a catalyst, the reaction can be carried out while keeping the atmosphere in the reaction system almost neutral, which is different from the conventional method. It is highly safe compared to other methods.

In addition, since it becomes possible to use industrially easily available α,β monounsaturated carboxylic acid compounds as raw materials, it is possible to provide industrially useful β-hydroxycarboxylic acid derivatives at low cost. I can do it.

EXAMPLES The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples.

Example 1 Preparation of 3-hydroxy-2-methyl-3-phenylpropionic acid dimethylamide 4 @cHo+cH = CH-CONMe22 12 (The molecular weight of C I2H 170 2 N is 207.) Benzaldehyde 106 (1 mmol) ,N,
120 μm (1.2 mmol) of N'-dimethylacrylamide and 130 μm (1.2 mmol) of phenylsilane were dissolved in 2 ml of 1,2-dichloroethane, and the system was replaced with an argon atmosphere.

To this solution was added 21 μm (0.05 mmol) of bis(dipivaloyl methanate) cobalt(II) at 20° C., and the mixture was stirred at the same temperature for 2 hours. After the reaction was completed, some of the volatile matter was distilled off under reduced pressure, and 5 ml of methanol and 2 ml of 2N monohydrochloric acid aqueous solution were added.
1 was added and stirred for 5 minutes.

Thereafter, it was poured into 20 ml of brine and extracted twice with ethyl acetate. The organic layer was washed with brine and then dried using anhydrous magnesium sulfate. Thereafter, the organic layer was concentrated and separated by thin layer chromatography (silica gel) to obtain 170 ml of the desired compound 4 (yield: 82%).

Note that 4 is diastereomer-4a. 4b,
The production ratio in this case was 1:4.

4a and 4b can be separated by thin layer chromatography.

Colorless oil CH3 4a (or 4b) Colorless oil 'H-NMR: (CDCI 3) δ=1. 02ppm (31!. d. J=7Hs
)2. 78-2. 82ppm (IH.m)2
．． 979llm (3ft.t) 3. 00ppm (3H, rich) 5.08pplI1 (2H br t)7. 20-7
．． 42Nm (5H, ra) I, R.
(Nest) 3300. 1645cm-'CH3 4b (or 4a) Colorless oil'H-NMR: (CDC7 3) δ=I. 22ppm (Hl.d.J=7Hs)
2. 86ppm (311.s) 2.89P9■ (3H.s) 3. 02-3. 211 ppm (IH.m) 4, 5
0ppm (IH br OH) 4. 80ppm (18 b++) 7. 20-7. 4299rn (511. ffl
)I. R, (Next) 330 [1.
11145cm-' Examples 2 to 9 3-Hydroxy-2-methyl-3-phenylbropio 4 In Example 1, the cobalt complex shown in Table 1 was used instead of bis(dipivaloyl methanate) cobalt [11]. The same procedure was followed except that the reaction temperature was changed to 20°C.

Quantification of the product was performed by gas chromatography.

In addition, the usage amount of the above compound 1 is 1 mmol, the usage amount of compound 2 is 1.2 mmol, the usage amount of compound 3 is 1.2 mmol, the usage amount of C o L 2 is 0.05 mmol, and the usage amount of C O L 2 is 0.05 mmol.
The amount of H2CH2Cl used was 2 ml.

Example 10 Preparation of 3-hydroxy-2-dimethyl-3-phenylprobionic acid dimethylamide Hydronic acid dimethylamide was obtained. Yield: 50% In addition, 17% of benzaldehyde was recovered, and 31% of benzyl alcohol (reduced product of benzaldehyde) was produced as a by-product.

The properties of the obtained compound and the results of instrumental analysis are shown below.

Colorless Oil 1 mmol of benzaldehyde, 1.2 mmol of methacrylic acid dimethylamide and 1.2 mmol of phenylsilane were dissolved in 2 ml of benzene.

This solution was charged into a reaction vessel, and the air in the reaction vessel was replaced with argon gas.

The temperature of the reaction solution was adjusted to 20°C, 0.05 mmol of bis(dipivaloylmethanato)cobalt(II) was added to the reaction solution, and the mixture was reacted at 20°C for 5 hours.

After 5 hours, post-treatment was carried out in the same manner as in Example 1, and 3-hydroxy-2-dimethyl=3-phenylprobio'H-N
MR: (CDCA' 3) δ=1. 20ppm (3tl.s.)■,
27ppm (3H.t) 3.03ppm (6tl, s) 4.82ppm (10, b r.s, OH)4.
95ppm (IH, s) 1.20-7.40ppm (5B.m) I.
R. (Nest) 3300, 1648an-
'Example 11 1 mmol of 3-hydroxy-2-dimethyl-3-phenylpropipenzaldehyde, 1.5 mmol of diisobutyramide methacrylate and 1.2 mmol of phenylsilane were dissolved in 2 ml of 1,2-dichloroethane.

This solution was charged into a reaction vessel, and the air in the reaction vessel was replaced with argon gas.

The temperature of the reaction solution was adjusted to 20°C, 0.05 mmol of bis(dipivaloylmethanato)cobalt (n) was added to the reaction solution, and the mixture was reacted at 20°C for 1 hour.

After 1 hour had passed, post-treatment was carried out in the same manner as in Example 1 to obtain 3-hydroxy-2-dimethyl-3-phenylpropionic acid diisopropylamide. Yield: 78% This was a mixture of diastereomers = 1:2.8.

In addition, 13% of benzyl alcohol (a reduced product of penzaldehyde) was produced as a by-product.

The properties of the obtained compound and the results of instrumental analysis are shown below.

Colorless oil 'H-NMR: (CDCA' 3) δ=1. Go~I. 50ppm (15H.m.)2.
10-3. 0OPIIOI (In, m)3.
90ppm (1B, Sepl*l I=7H!) 4,7
0~4.82ppm (H.a) 5.05~5.18
ppm(H.br.s,OH)7.20-7.50
pp Tsuru (SH.m) 1, R, (N...) 3300. 1
648cm-' Example 12 Preparation of 3-hydroxy-2-methyl-5-phenyl-4-bentenoic acid dimethylamide 3-hydroxy-2-methyl-5-phenyl-4-pentenoic acid dimethylamide was obtained. The yield was 296%. The mixing ratio of diastereomers was 1:2.6.

The properties of the obtained compound and the results of instrumental analysis are shown below.

1 mmol of colorless oil cinnamaldehyde, 1.2 mmol of acrylic acid dimethylamide and 1.2 mmol of phenylsilane were dissolved in 2 ml of EDC (ethylene dichloride).

This solution was charged into a reaction vessel, and the air in the reaction vessel was replaced with argon gas.

The temperature of the reaction solution was adjusted to 20°C, 0.05 mmol of bis(dipivaloylmethanato)cobalt(II) was added to the reaction solution, and the mixture was reacted at 20°C for 4 hours.

After 4 hours, post-treatment was carried out in the same manner as in Example 1, and among the CH3 diastereomers, ■'H-NMR: (CDCj,) δ=1. 19ppm (3H. d. J=711
! ) 2.809lll (IH.d.q.J=7H!sI
ld 2H! )2. 979pm (38, s) 3. 0611PI (3H, s) 4. 66ppm (IH. d. I=2HX)4.
89ppm (IH, br.t. (011))6
．． 16ppm (11.d.d.J=I6Hs
snd 4Ht) 6.71ppm (II.d, J=16
Ht)7. 20-7. 45911m (511,
m. )! , R. (Neat) 339L
Among the 1617an-'diastereomers, ■'H-NMR: (CDCl3) δ- 1. 22ppm 3H. d. J=7H! )2
．． 26ppm IH. L J=7H! )2. 94
ppll+31, s) 3.04ppm 3■. 0 4. 32ppm 21 bt, s. )6.22p
pm IH. d, d, J=16Ht 1++d 6Hx
)6. 63ppm It{, d. J:16Hx)
7. 18-7. 42ppm (511, m.)1,
R, (Next) 3396, 1624a
n-' Examples 13 to 15 The same procedure as in Example 12 was carried out except that the carbonyl compound listed in Table 2 was used instead of cinnamaldehyde and the reaction time was changed as listed in Table 2.

Table 2 shows the types and yields of the β-hydroxycarboxylic acid derivatives obtained.

The analytical data of the compounds obtained in Examples 13 to 15 shown in Table 2 above are shown below.

Example 13 Among the diastereomers, ■'H-NMR: CCDCI 3) δ=I. llppII+(3H.d. J=71{
! )1. 36ppm (3H.s) 2. 769H (IH.Q.J.7 old)3. 0
ippm(3}1.s) 3. l1tlH(3}1, s) 5. 59ppffi (IH.br.s, )5.
04ppm (IH. d. J=6H!)6. 7'
4ppm (18.d, J=6Ht)7. 18
~7. 44ppm (5H.m.)1. R
．． (NeN) 3390. 1621an-' diastereomer ■ 'H-NMR: (CDCl3) δ=t. 27ppm (3H.d, J=7}1
! )1. 32ppm (3H.s) 2. 86ppm (3H.s) 3.04ppm (38,s) 5.62ppm (IH,s) 6.22ppm (18.d. J=6H!)6. 6
1ppm (IH. d. ] = 6H!) 7.18~1
．． 44ppm (5H, m.) 1, R, (N…)
33!12. 1624cm-'Example 14 Diastereomers ■'H-NMR: (CDCj 3) δ=1. 34ppm (3H, d. J=7H!
)1. 46ppm+(3H, t) 2. fi4pp+a (38, s)2. 79pp
m (3H.s) 3. 16ppm (1B.+.J=711!)6.
02ppa+(1B.l.(ott))7.15~
? ．． soppffi (5M, m.) Diastereomer ■'H-NMR: (CDCj 3) δ=0. 87ppa+(3+1.d.J=7H
s)1. 52ppm (3H.s) 2.99ppm (IH.L J=71{x) 3.03p
pm (3H.s) 3. 1411111 (311.1) 5.919pm (IH.s.(OH)) 7, 20-7.
SQppm (SH.m.) Example 15 lH-NMR: (CD(1 3) δ= 1.21ppm (3tl.d.J=7H!
)1. 30-2. 12ppm (9H.m)2.
35-2. ? Oppm (IH, m)2. 98tl
Pm (3H.s) 3. 09tllll1 (3H, s) 4. 97ppm (10.s) 7.15-7. 40ppm (5H.m.)1
．． R. (Nest) 3300. 1624
cm-' Example ■6 3-hydroxy-2-methyl-3-phenylpropio@
Umino + cH2 = CH-Co2Me 0 H C H 3 In Example 1, acrylic acid methyl ester was used instead of acrylic acid dimethylamide, and the reaction time was 20
The procedure was the same except that the time was changed.

By carrying out the reaction as described above, 3-hydroxy-2
-Methyl-3-phenylpropionate was obtained with a yield of 72%. The diastereomeric ratio of this compound is 1
:1.4.

In addition, 14% benzyl alcohol was produced as a by-product.

The properties of the obtained compound (mixture of diastereomers) and the results of instrumental analysis are shown below.

Colorless oil CH3 A chart of the 'H-NMR spectrum of the resulting compound is shown in Figure 1 (measured in CDCl3).

In addition, the results of infrared spectrum measurement of this compound (N
...), 3456C111-' and 1743ao-' specific peaks were observed.

Example 17 3-Hydroxy-2-ethyl-5-phenyl-4-peneCH3 1.2 mmol of phenylsilane and 0.05 mmol of bis(dibivaloylmethanato)cobalt (If) in EDC2
ml and heated to 50°C under an argon atmosphere.

A solution prepared by dissolving 1 mmol of cinnamaldehyde and 1.2 mmol of crotonic acid dimethylamide in 1 ml of EDC was gradually added dropwise to this solution. Thereafter, the mixture was reacted at 50°C for 5 hours. After the reaction was completed, post-treatment was carried out in the same manner as in Example 1,
The title compound was obtained. Yield: 7.2% The mixing ratio of diastereomers was 1:2.

The analytical data of the obtained compound is shown below.

Among diastereomers, ■'H-NMR: (CDCJ 3) δ=0. 91ppm (3H.t.J=7Ht
)1. 80ppm (2[1.d.q.J=7
Old sIId 2H! )2. 78 ~2. 90ppm
(IH.m)3. 0011111 (38.s) 3. 109pm (3H. wealth) 4. 53ppa+(Ill. br, s.(OH)
)4.54-5. 58tltll(IH,m)6.6
2991 (IH.dd.J=14Ht wad 41
1x)6. 69ppm (1[1, d, J=14
Ht) 7.20-7. 54ppm (SR. I1.
)1. R. (N...) 3394, 1622an-'
Among the diastereomers, ■'H-NMR: CCDCI 3) δ=0. 97pn (3H.t.J=7Hs)1
．． 75-1. 90ppm (IH, m) 2.76~
2. 90ppm (IH.m) 2.96ppm (Hl,
s) 3. 04ppm (311.s) 4. 41ppm (2H.bt.s) 6.199I
lm(IH, d.dl=16Hx xnd 6[1!)
6. 83ppm (IH. d. J=l6Hs)7.
20-7. 45ppm (51{.II.)1,
R. (N…) 33N. ! 622cm-'Example 18 Production of 3-hydroxy-2-methyl-5-phenyl-4-pentenoic acid methylphenylamide OH CJ O C611s In Example 1, acrylic acid methylphenylamide was used instead of acrylic acid dimethylamide. , reaction time 2
The same operation was performed except that the time was changed to 0 hours.

By carrying out the reaction as described above, the title compound 6
Obtained with a yield of 2%.

The diastereomer ratio of this compound was 1:4.

'H-NM of the diastereomer mixture obtained in Figure 2
A chart of R is shown.

Example 19 Production of 3-hydroxy-2-methyl-5-phenyl-4-bentenoic acid methyl ester The procedure of Example 16 was repeated except that cinnamaldehyde was used instead of benzaldehyde.

The title compound was obtained in 80% yield.

The diastereomer ratio was approximately 1ζ1.

The properties and instrumental analysis results of the obtained compound (mixture of diastereomers) are shown below.

A 'H-NMR chart of this compound is shown in FIG.

In addition, the results of infrared spectrum measurement of this compound (N
...), specific peaks were observed at 3466 CII1-' and 1725 cm-'.

[Brief explanation of the drawing]

Figure 1 shows the 3-hydroxy-2- obtained in Example 16.
'H-NM of methyl methyl-3-phenylpropionate
It is a chart of R spectrum. Figure 2 shows the 3-hydroxy-2- obtained in Example 18.
It is a chart of the 'H-NMR spectrum of methyl-5-phenyl-4-bentenoic acid methylphenylamide. Figure 3 shows the 3-hydroxy-2-
It is a chart of 'H-NMR spectrum of methyl-5-phenyl-4-pentenoic acid methyl ester.

Claims (2)

[Claims] (1) Cobalt complex of β-dicarbonyl compound represented by the following formula [I]; ▲There are mathematical formulas, chemical formulas, tables, etc.▼...[I] [In the above formula [I], R^1, R^ 2, R^4 and R^5 are each independently a hydrogen atom, a carbon number of 1 to
Represents an atom or group selected from the group consisting of 10 lower alkyl groups, cycloalkyl groups, aryl groups, arylalkyl groups, trifluoromethyl groups, alkoxycarbonyl groups, and carbamoyl groups, R^3 and R^6
Each independently represents a group selected from the group consisting of a lower alkyl group, an aryl group, an arylalkyl group, and a cycloalkyl group having 1 to 10 carbon atoms. ]Using,
α,β-unsaturated carboxylic acid derivative represented by the following formula [II]; ▲There are mathematical formulas, chemical formulas, tables, etc.▼...[II] [However, in the above formula [II], R^7, R^8 and R^9 each independently represent a hydrogen atom or a lower alkyl group having 1 to 10 carbon atoms, and X is a hydrogen atom or a lower alkyl group having 1 to 10 carbon atoms.
Lower alkoxyl group, phenoxy group, amino group, alkylamino group (▲Mathematical formulas, chemical formulas, tables, etc. are available▼) (
However, in the formula, R^1^2 and R^1^3 each independently represent an atom or group selected from the group consisting of a hydrogen atom, a lower alkyl group having 1 to 10 carbon atoms, and an aryl group,
R^1^2 and R^1^3 may be linked to each other to form a ring) and an arylalkyl group]; Represented by the following formula [III] Carbonyl compound; ▲ Formula,
There are chemical formulas, tables, etc. ▼...[III] [However, in the above formula [III], R^1^0 and R^1^1 each independently represent a hydrogen atom, a carbon number of 1 to 2
0 represents an atom or group selected from the group consisting of an alkyl group, an aryl group, an arylalkyl group, an alkenyl group, and a cycloalkyl group, and R^1^0 and R^1^1 are connected to each other to form a ring. A method for producing a β-hydroxyl carboxylic acid derivative represented by the following formula [IV], which is characterized by reacting [IV ] [However, in the above formula [IV], R^8 ~ R^1^2
has the same meaning as above]. (2) After reacting the α,β-unsaturated nitrile compound, carbonyl compound, and phenylsilane, the phenylsilane is separated from the reaction product by hydrolysis or solvent decomposition. β-
Method for producing hydroxyl carboxylic acid derivative;