Asymmetric Synthesis Using Chiral Lewis Base

手性路易斯碱指向金属试剂的金属中心并激活试剂。因此，极有可能通过手性路易斯碱与金属的配位来实现反应的立体化学控制。然而，在现代合成化学中，手性路易斯碱在反应中的使用是相当罕见的。这与我们熟悉的手性路易斯酸作为激活剂和立体控制器形成鲜明对比。本文主要研究了手性路易斯碱的设计、合成及其在不对称合成中的应用。此外，我们将手性路易斯碱作为手性催化剂应用于该反应中，可以产生比手性催化剂更具有光学活性的化合物。作为研究的结果，我们开发了如下所示的相当有希望的反应。手性氨基醚催化下烯酸锂与亚胺不对称合成ee大于90%的β -内酰胺用手性氨基醚催化量催化不对称合成高旋光性β -内酰胺。有机锂与亚胺反应催化不对称合成ee含量大于90%的胺。这些有希望的结果将为合成有机化学及其在工业生产中的应用开辟一个新的领域。

Chiral Lewis base coordinates to metallic center of metallic reagents and activates the reagent. Consequently, it is highly probable that stereochemical control of the reaction would be achieved by coordination of the chiral Lewis base to metal. However, the use of chiral Lewis base in the reaction is quite rare in the modern synthetic chemistry. This is clearly contrasted to the familiar use of chiral Lewis acid as activator as well as stereoconytoller.In the present research we focused on design, synthesis, and application of chiral Lewis base into asymmetric synthesis. Moreover, we applied the chiral Lewis base as a chiral catalyst in the reaction which can produce optically active compounds more than the equivalence of the chiral catalyst.As a result of the studies we developed quite promising reactions as shown below.1. Asymmetric synthesis of beta-lactam of more than 90% ee by the reaction of lithium ester enolate with imine in the presence of chiral amino ether catalyst.2. Catalytic asymmetric synthesis of highly optically active beta-lactam using catalytic amount of chiral amino ether.3. Catalytic asymmetric synthesis of amines of more than 90% ee by the reaction of organolithium with imines.These promising results may open a new world of synthetic organic chemistry and its application to the industrial production.