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.

通过羰基化合物的去质子化来制备烯醇，并且是有机合成中重要的中间体，可以通过与各种电率的反应提供多种产物。本研究的目的是设计和合成各种旋转性手性胺，并设计方法，以有效地映射性的不体烷基化和质子化的脂质烯醇化和质子化直肠，并使用这些手性多端的胺作为触角辅助物。本研究的最终目的是使这些反应催化对所使用的手性胺。（1）催化不对称的烷基化：对映射性不对称的不对称烷基化的检查，对型锂的映射不对称的烷基化构巩固了通过对cyclohexanone and interions sor reation sor reation的构造的构造制备的构构制备的，这是对cy的反应的反应。多齿胺通过使用二齿胺进行了检查，而使用四齿手性胺则很高。基于这一发现，使用0.05在存在2当量的二态性无胺等效物的情况下，使用0.05等于四烯酸胺的催化不对称烷基化反应。为了实现催化性锂烯醇的催化不对称质子化，进行了检查，以非常缓慢地将质子源添加到反应混合物中，以缓慢地将锂烯醇固化。现在表明，可以通过类似于上述催化不对称烷基化的反应条件有效地进行催化性锂烯醇的催化不对称原型。