Catalytic Asymmetric Formation and Reactions of Lithium Enolates and Elucidation of their Mechanisms

烯醇化锂的形成和反应是合成有机化学中常用的最基本的过程。我们以前报道过新的对映选择性不对称去质子化、烷基化和质子化反应。本研究的目的是使这些对映选择性不对称反应催化不对称反应的手性胺作为手性助剂。为了使这些反应具有催化不对称性，有必要找出受手性助剂影响的反应比不受手性助剂影响的反应进行得更快的条件。基于对这些反应机理的研究，我们考察了满足这些条件的各种可能性。前手性羰基化合物的对映选择性不对称去质子化反应。我们发现双齿手性锂酰胺的去质子化速率比三齿性锂酰胺快。我们还发现手性双齿胺和非手性三齿锂酰胺之间的原位锂氢交换反应发生迅速，有利于任何一方的形成，这取决于这两种物质的结构。因此，利用少于化学计量量的手性双齿胺和多于化学计量量的具有适当结构的非手性三齿锂酰胺的组合，首次实现了手性双齿胺的催化不对称去质子化反应。在前手性烯醇酸锂的对映选择性不对称烷基化反应中，我们发现在双齿胺的存在下烷基化速率没有提高，而在四齿胺的存在下烷基化速率有一定提高。因此，期望四齿手性胺和双齿非手性胺之间与锂的快速配体交换反应，首次使用少于化学计量量的手性四齿胺和多于化学计量量的非手性双齿胺的组合实现了催化不对称烷基化反应。同样的策略被成功地应用于催化不对称质子化反应。少

Formation and reactions of lithium enolates constitute the most fundamental processes frequently employed in synthetic organic chemistry. We have previously reported novel enantioselective asymmetric deprotonation, alkylation, and protonation reactions. The purpose of the present research is to make these enantioselective asymmetric reactions catalytically asymmetric reactions as to the chiral amines used as chiral auxiliaries.To make these reactions catalytically asymmetric, it is necessary to find out conditions in which the reactions influenced by chiral auxiliaries proceed reasonably faster than those not influenced by chiral auxiliaries. Based on the studies on the mechanisms of these reactions, we examined various possibilities that satisfy such conditions.In enantioselective asymmetric deprotonation reactions of prochiral carbonyl compounds. we have found that the rates of deprotonation by bidentate chiral lithium amides proceed faster than those by tridentate lithium amides. We … More have also found that in situ lithium-hydrogen interchange reactions between chiral bidentate amine and achiral tridentate lithium amides occur rapidly favoring the formation of either sides, depending on the structures of these two species. Thus, using a combination of less than a stoichiometric amount of chiral bidentate amines and more than a stoichiometric amount of achiral tridentate lithium amides having appropriate structures, catalytic asymmetric deprotonation reactions as to the chiral bidentate amines were realized for the first time.In the enantioselective asymmetric alkylation reactions of prochiral lithium enolates, we have found that the rates of alkylation in the presence of bidentate amines are not enhanced, while those in the presence of tetradentate amines are reasonably enhanced. Thus, expecting fast ligand exchange reactions to the lithium between tetradentate chiral amines and bidentate achiral amines, catalytic asymmetric alkylation reactions were realized for the first time using a combination of less than a stoichiometric amount of chiral tetradentate amines and more than a stoichiometric amount of achiral bidentate amines. The same strategy was successfully applied to catalytic asymmetric protonation reactions. Less