JPH0525864B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention provides an optically active secondary compound having a high degree of optical purity.
This invention relates to the production of alcohols by catalytic asymmetric broadening synthesis. The catalytic asymmetric broadening synthesis method refers to a reaction that provides a reaction product having an optical purity several times higher than that of the optically active compound used as a catalyst, and was discovered by the present inventor. [Prior Art] There have been many reports that secondary alcohols with a high degree of optical purity can be synthesized by asymmetric reduction reactions of special ketone compounds. Almost all of these methods use an optically active compound, a reducing agent, and a substrate in a stoichiometric manner, and are not commercially profitable and have not been adopted. It has been reported that optically active secondary alcohols can also be synthesized by the reaction of an aldehyde compound with a typical organometallic compound having an optically active ligand at a low temperature such as -78°C, but this is not practical. Ta. [Problem to be solved by the invention] Asymmetric catalytic reactions that produce large amounts of optically active compounds with high optical purity using small amounts of optically active catalysts are a dream of humankind, and organic chemists have actively researched them in the past. have been tried, but there are very few success stories. The present invention is the first example of a highly catalytic asymmetrically enriched alkylation reaction of aldehyde compounds. Many typical organometallic compounds are known, but
Most react with aldehyde compounds, but dialkylzincs do not react in nonpolar solvents;
The present inventor has discovered that a Lewis base such as amine and amine can act as a catalyst to cause a reaction between the two. As a result of extensive research using this reaction unique to dialkylzinc, we found that optically active secondary alcohols can be synthesized by catalytic asymmetric reactions when optically active β-amino secondary alcohols are used as catalysts. discovered and published in an academic journal (Tetrahedron
Letters 25, 2823 (1984)). However, the optical purity of the optically active alcohol obtained at that time was 48% at most.
However, there were few practical applications. Subsequent research by the present inventors revealed that the asymmetric yield was dramatically improved by dialkylating the amino group of the β-amino secondary alcohol of the catalyst containing a heterocycle such as a piperidyl group, and that the asymmetric yield was dramatically improved. This led to the invention that an optically active secondary alcohol with high optical purity can be synthesized by increasing the bulk of an alkyl group such as a tertiary butyl group. [Means for Solving the Problems] The gist of the present invention is to combine aldehydes represented by the following general formula () R ¹ CHO () (where R ¹ CHO represents an aromatic aldehyde) and the following general formula ( ) R ² ₂ Zn ( ) (However, R ² includes aliphatic and alicyclic alkyl groups) Using the following general formula () as a catalyst, (However, R ³ represents a bulky substituent,

〔Example〕

The present invention will be further explained below with reference to Examples, but the present invention is not limited thereto in any way. Note that in Example (2) and subsequent operations, the operations are the same as in Example (1), and only the raw materials and products used are different, so they are shown in a list. Reference example (catalyst production example) Production of optically active (-) 1-piperidyl-3,3-dimethylbutanol-2 This compound is synthesized as a racemate by the chemical reaction formula below, and is combined with dibenzoyltartaric acid (optically active). Optical resolution was achieved by salt recrystallization. [α] ²² _D −71.5° (ethanol) The overall yield was 75%. Example 1 A hexane solution (1.5) of optically active (-) 1-piperidyl-3,3-dimethylbutanol-2 (18 mmol) with an optical purity of 98% was placed in a reaction vessel under a nitrogen stream.
Add diethylzinc (0.91mol) and heat at 30°C.
The mixture was reacted for 1 hour. The solution was cooled to 0° C. and benzaldehyde (0.9 mol) was slowly added.
After 18 hours, the reaction solution was slowly added to dilute aqueous hydrochloric acid solution (1) and stirred. The hexane layer was separated and the hexane was removed by distillation to obtain 1-phenylpropanol ([α] ²⁵ _D = -39, in 9° ethanol) with optical purity of 99% in a yield of 95%. Examples 2 to 5 Asymmetric broadening reactions were carried out under the same reaction conditions as in Example 1, and the results are summarized in Table 1 below.

[Table] Examples 6 to 11 Examples of asymmetric broadening reactions between other aldehydes and diethylzinc are summarized in Table 2 below.

[Table] Determined by liquid chromatography.
[Effects of the Invention] The present invention is a very effective reaction for producing pharmaceuticals, agricultural chemicals, and other fine chemicals. It is a constituent substance.

Claims (1)

[Claims] 1 Aldehydes represented by the following general formula () R ¹ CHO () (where R ¹ CHO represents an aromatic aldehyde) and the following general formula () R ² ₂ Zn () (where R ² contains aliphatic and alicyclic alkyl groups) and a dialkylzinc represented by the following general formula () as a catalyst. (However, R ³ represents a bulky substituent,
[Formula] represents a heterocycle formed with N) The following general formula () is characterized by being reacted and hydrolyzed in the presence of an optically active β-amino secondary alcohol represented by (However, R ¹ and R ² are the same as above)
A method for catalytic asymmetric broadening synthesis of alcohols. 2. The synthesis method according to claim 1, wherein the optically active β-amino secondary alcohol represented by the general formula () as a catalyst is 1-piperidyl-3,3-dimethylbutanol-2. 3. The reaction between aldehydes represented by the general formula () and dialkylzinc represented by the general formula () is carried out from 0 to
A method according to claim 1, which is carried out at a relatively high temperature of 30°C.