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Catalytic Asymmetric Alkylation and Protonation of Lithium Enolates

烯醇锂的催化不对称烷基化和质子化

基本信息

批准号：
12470478
负责人：
KOGA Kenji
金额：
$ 6.4万
依托单位：
Nara Institute of Science and Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

Enolates are prepared by deprotonation of carbonyl compounds, and are important intermediates in organic synthesis to give a variety of products by the reactions with various electro-philes. The purpose of the present study is to design and synthesize various mutidentate chiral amines, and to devise methods to carry out efficiently enantioselective asymmeric alkylation and protonation rectons of achiral lithium enolates using these chiral multidentate amines as chiral auxiliries. The final object of the present research is to make these reactions catalytic as to the chiral amines employed.(1) Catalytic Asymmetric Alkylation : Examinations on the enantioselective asymmetric alkylation of prochiral lithium enolates prepared by deprotonation of cyclohexanone and 1-tetralone have shown that the chemical yields of the reactions are highly dependent on the coordination numbers of the chiral multidentate amines examined, lower by using bidentate amines, while very high by using tetradentate chiral amines. Based on this finding, catalytic asymmetric alkylation reaction was realized by using 0.05 equivalent of a tetradentate chiral amine in the presence of 2 equivalents of a bidentate achiral amine.(2) Catalytic Asymmetric Protonation : Proton is an electrophile, and protonation reaction of lithium enolates is known to be a very fast reaction. To realize catalytic asymmetric protonation of prochiral lithium enolates, examinations were made to protonate the lithium enolates slowly by adding proton source to the reaction mixture very slowly. It is now shown that catalytic asymmetric protoantion of prochiral lithium enolates can be carried out efficiently by the reaction conditions similar to those described above for catalytic asymmetric alkylation.

烯烃类化合物是由羰基化合物去质子化得到的，是有机合成中的重要中间体，通过与各种亲电性的反应得到各种产物。本研究的目的是设计和合成各种手性多齿手性胺，并利用这些手性多齿胺作为手性助剂，设计出有效地进行非手性锂烯醇酸酯的不对称烷基化和质子化反应的方法。本研究的最终目的是使这些反应对所使用的手性胺具有催化作用。(1)催化不对称烷基化：通过环己酮和1-四酮的去质子化制备的前手性锂的不对称烷基化反应的研究表明，反应的化学产率高度依赖于所考察的手性多齿胺的配位数，使用双齿胺的反应的化学产率较低，而使用四齿的手性胺的反应的化学产率很高。基于这一发现，在双齿无手性胺的存在下，使用0.05当量的四齿手性胺实现了催化不对称烷基化反应。(2)催化不对称质子化反应：质子是亲电试剂，而锂烯醇酸盐的质子化反应是非常快的反应。为了实现前手性烯醇酸锂的催化不对称质子化，通过在反应混合物中缓慢地加入质子源，对烯醇酸锂进行了缓慢质子化实验。结果表明，在类似于上述催化不对称烷基化反应的反应条件下，前手性锂烯醇酸酯的催化不对称原氨化反应可以有效地进行。