JPH02102743A - Production of catalyst for coupled addition reaction and 1,5-dicarbonyl compound - Google Patents

Abstract

PURPOSE:To obtain a catalyst for a coupled addition reaction under neutral conditions by using an organotin compd. having a specified compsn. CONSTITUTION:An organotin compd. represented by a general formula RnSn(OSO2CF3)4n (where R is alkyl group or aryl group and n is 1-3) is used as the catalyst for the coupled addition reaction. This catalyst brings a nucleophilic agent such as enolsilylether into the coupled addition reaction to an alpha,beta-unsatd. carbonyl compd. such as methyl vinyl ketone. The reaction is allowed to proceed under nearly neutral conditions and a 1,5-dicarbonyl compd. can be produced by simple operation.

Description

Detailed Description of the Invention <Industrial Application Field> The present invention relates to a conjugate addition reaction catalyst and a method for producing a 1,5-dicarbonyl compound, and more specifically to a conjugate addition reaction comprising an organic tin trifluoromethanesulfonate derivative. This invention relates to catalysts and methods for producing compounds useful as intermediates in the production of fragrances and pharmaceuticals using the catalysts.

The conjugate addition reaction catalyst provided by the present invention is α of enol silyl ether or ketene monosilyl acetal,
β-Unsaturated carbonyl compounds promote addition reactions. These reactions yield 1,5-dicarbonyl compounds useful as intermediate raw materials for the production of perfumes and pharmaceuticals. 1,5-
Typical examples of dicarbonyl compounds include prostaglandin precursors such as 3-acyl-1-cyclopentanone.

<Prior Art> Conventional conjugate addition reactions of α,β-unsaturated carbonyl compound nucleating agents have been carried out under strongly basic conditions. Therefore, there was a restriction that it could not be applied to raw materials that are unstable under strong basic conditions, which will be described later. In order to compensate for this drawback, it has been proposed to use organosilicon compounds such as enol silyl ether and ketene monosilylacetal [Angevante et al.
89, p. 858 (1977)], but these reactions require the use of a Lewis acid such as Ti (44 or AQCfJ) in a stoichiometric amount.

<Problems to be Solved by the Invention> In order to conjugately add various nucleophiles to α,β-unsaturated carbonyl compounds by conventional methods, substrates and reactants having functional groups sensitive to bases and acids are required. Therefore, there has been no successful example of conjugate addition to 2-cyclobentenone, which is extremely important as an intermediate for pharmaceutical production. Furthermore, methyl vinyl ketone, which easily polymerizes, cannot generally be used. Therefore, the object of the present invention is to proceed with the conjugate addition reaction under mostly neutral conditions, thereby achieving the above-mentioned problems that were previously impossible. The object of the present invention is to provide a catalyst that enables various reactions.

<Means for Solving the Problems> According to the present invention, the above object is achieved by the general formula % (1) (wherein R represents an alkyl group or an aryl group, and n represents a number from 1 to 3). This can be achieved by using an organic tin trifluoromethanesulfonate represented by the following as a conjugate addition reaction catalyst.

In the above general formula, R represents an aliphatic alkyl group such as a methyl group, an ethyl group, a propyl group, a butyl group, or a pentyl group, an unsaturated alkyl group such as an allyl group or a crotyl group, or an aryl group such as a phenyl group or a P-tolyl group. represents a group. n
represents 1 or 2 or 3.

The compound represented by the general formula (1) is considered to be completely new as an organic reaction catalyst, particularly as a conjugate addition reaction catalyst. In addition, 1 obtained by conjugate addition reaction,
Naturally, the manufacturing method using the organotin compound described in (1) above as a catalyst in the synthesis of a 5-dicarbonyl compound is also novel.

Examples of the α,β-unsaturated carbonyl compounds used in the method for producing 1,5-dicarbonyl compounds of the present invention include α,β-unsaturated carbonyl compounds such as methyl vinyl ketone, ethyl vinyl ketone, 2-cyclopentanone, and 2-cyclohexanone. , β−
, α, β-, β-aldehydes such as β-ketone, acrolein, methacrolein, crotonaldehyde, α, β-unsaturated carboxyl esters such as acrylic acid ester, crotonic acid ester, Nisder methacrylate.

The enol silyl ether used in the present invention has the general formula (
■) is represented by ■.

Ketene monosilylacetal is represented by general formula (10).

(In the formula, R1, R2, +3.R4 represent an alkyl group such as a methyl group or an ethyl group, or an aryl group such as a phenyl group or a P-tolyl group.) In the above conjugate addition reaction, one of the conjugate addition reaction catalysts of the present invention (1) is 0 for α,β-unsaturated carbonyl compounds.
．． It is used in an amount of 1 to 50 mol%, preferably 1 to 10 mol%. The conjugate addition reaction uses an organic solvent,
Particularly preferably, the reaction is carried out in the presence of a hydrocarbon solvent such as hexane or toluene, or a halogenated hydrocarbon solvent such as methylene chloride or 1°2-dichloroethane, usually at a temperature of -78°C to 30°C.

The organotinfluoromethanesulfonate (1) used in the present invention is described in the literature [for example, Hemische Berichte (C
Volume 103, Volume 8
68 (1970)].

<Function> Since the organotin triple olomethane sulfonate used as a catalyst in the present invention exists stably in the air, it is particularly difficult to dehydrate and dehydrate during the production process of 1,5-dicarbonyl compounds, which is an application of conjugate addition reaction. It is extremely easy to handle as it does not require any treatment such as air, and furthermore, because of its low acidity, the reaction can be carried out under extremely neutral conditions. Therefore, even if the raw materials or products are unstable, the desired product can be suitably produced.

<Examples> The present invention will be specifically described below with reference to Examples, but the present invention is not limited to these Examples.

Example 1 2-cyclobentenone (82■, 1 mmof), α-
Trimethylsiloxystyrene (0, 26mQ, 1
, 3 mm off), dibutyltin bis(trifluoromethanesulfonate) (53@, 0.1 mmoΩ), and toluene (5-) at 78°C to 0°C.
Stir for hours. After adding a saturated aqueous sodium hydrogen carbonate solution, the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated. The obtained residue was dissolved in THF (5
-) and IN 1 (CG(1-) and stirred at room temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate, The resulting residue was purified by silica gel column chromatography to obtain 2-phenacylcyclopentanone having the following physical properties (96μ, yield 51%).

EINS spectrum 202(P) NMR spectrum (100MHz) δTen9, 1.2-2
．． 9 (m, 7H).

3.13 (s+, 2H), 7.49 (m, 3H), 7.
96 (m, 2) 1) Examples 2 to 7 As shown in the first half of Table 1, a cycloalkenone of a specified type,
A mixture of enol silyl ether, 10 mol% dibutyltin bis(trifluoromethanesulfonate), and a solvent was stirred for a predetermined time at a predetermined humidity.The reaction mixture was treated with IN HCΩ-TIIF for 30 minutes at room temperature, and the resulting residue was M”r by silica gel column chromatography
By doing so, the corresponding 1,5-diketones were obtained. The results are shown in the second half of Table 1.

Example 8 In Example 1, instead of α-trimethylsiloxystyrene, 1-1-butoxy-(mut-butyl-5-dimethylsiloxy)etheno(0,35+Jl, ?, 3+mmoll)
) was reacted in the same manner as in Example 1, except that butyltin tris(trifluoromethanesulfonate) (62 mg, 0.1 mmoff) was used instead of dibutyltin bis(trifluoromethanesulfonate) and the reaction was carried out at -78°C for 5 hours. By performing post-treatment and separation and purification, 2-(↓-butoxycarbonylmethyl)-cyclopentanone (152 mg, 72%) having the following physical properties was obtained.

EI NS spectrum 198 (M”) NMR spectrum (100 MHz) δY&, 1.45 (S, 9H)
.

1.7-2.6 (■, 9H) Examples 9-11 As shown in Table 2, predetermined amounts of cycloalkenone, ketene monosilylacetal, 10 mol% dibutyltin bis(trifluoromethanesulfonate), and A reaction mixture obtained by reacting a mixture of solvents at a predetermined temperature for a predetermined time was treated with IN HCQ-THF at room temperature for 30 minutes, and then separated and purified using silica gel column chromatography to obtain the corresponding 5-ketoesters. . The results are shown in the second half of Table 2.

Example 12 Same as Example 1 except that methyl vinyl ketone (70 mm, 1 mm off) was used for the aroma of 2-cyclobentenone, methylene chloride was used instead of toluene, and the reaction was carried out at -78°C for 2 hours. By performing 1 reaction, post-treatment, and separation and purification in the same manner, 1 with the following physical properties was obtained.
-Phenyl-1,5-hexanedione (181■, 95
%) was obtained.

EI NS spectrum 190 (M”) NMR spectrum (100 MHz) δ & 9, 2.04 (m, 2) I
).

2.14 (S, 38), 2.57 (t, J = 6.8Hz
, 2H), 3.0L (t, J=7.0Hz, 2H), 7
．． 51 (m, 3) 1), 7.97 (m, 2H) Example 1
3-17 As shown in the first part of Table 3, a predetermined amount of α, β-unsaturated ketone, enol silyl ether or ketene monosilyl acetal, 10 mol % of dibutyltin bis(trifluoromethanesulfonate), and a mixture of a solvent are predetermined. The reaction was carried out at a specified temperature for a certain period of time.

The reaction mixture was treated with IN ) lcff-THF at room temperature for 30 minutes, and then separated and purified by silica gel column chromatography to obtain the corresponding 1,5-diketone bodies. The results are shown in the second half of Table 3.

Example 18 In Example 1, t instead of 2-cyclobentenone
rans-2-hexenal (98 mg, 1 mn+o
Q).

1 at -78℃ using methylene chloride instead of toluene.
By carrying out the reaction and post-treatment 1 separation and purification in the same manner as in Example 1 except for reacting for a certain time, 3-phenacylhexanal (111■, St%) having the following physical properties was obtained.
I got it.

[! I NS spectrum 218 (M”) NMR spectrum (100 MHz) δP&, 0.90 (t, J=
6.3Hz, 3H), 1.38 (m, 5H), 2.5
2 (a+, 2H), 3.00 (m, 2H).

7, 49 (m, 3t (), 7.49 (++, 3H)
, 7.95 (m, 2H), 9.77 (S, 0
1) Example 19 In Example 1, methyl crotonate (loomg, 1mmoQ) was used instead of 2-cyclobentenone, and 1-methoxy 2 was used instead of α-trimethylsiloxystyrene.
-Methyl-1-trimethylsiloxy-1-propene (2
27■, 1.3 Otori mob), t) The following reaction was carried out in the same manner as in Example 1, except that methylene chloride was used instead of renin and the reaction was carried out at -78°C for 2 hours. Methyl 4-methoxycarbonyl-2,2,3-trimethylbutanoate (61■,
30%).

EI MS spectrum 202 (M”) NMR spectrum (100M) Iz) δ 9, 0.80 (d, J=
6.2Hz, 3H), 1.02(S, 6H), 1.1
(m, 1N), 2.0 (+, 2H).

3.46 (S, 6H) <Effects of the Invention> By using the catalyst of the present invention, 1,5-dicarbonyl compounds, which were previously impossible to produce, can be produced by simple operations under extremely mild conditions. This is a major contribution to the production of fragrances and pharmaceuticals.

that's all Deko Roku Daiji Temple Junkura

Claims (1)

[Claims] 1 General formula R_nS_n(OSO_2CF_3)_4_
A conjugate addition reaction catalyst comprising an organotin compound represented by -_n (wherein R represents an alkyl group or an aryl group, and n represents a number from 1 to 3). 2. A method for producing a 5-dicarbonyl compound, which comprises carrying out a conjugate addition reaction of a nucleophile to an α,β-unsaturated carbonyl compound in the presence of an organic solvent and the catalyst according to claim 1. 3. The method for producing a 1,5-dicarbonyl compound according to claim 2, wherein the nucleophile is an enolsilyl ether or a ketene monosilyl acetal.