Novel Ruthenium Catalysts for Metathesis Stereocontrol

描述(由申请人提供)：由于立体异构体表现出的生理特性的多样性，现在要求在合成药效团时进行对映选择性和非对映选择性控制。尽管烯烃歧化化学已经经历了发展Ru亚烷基催化剂的复兴，但一般的立体化学控制仍然是一个挑战。这项建议概述了一种新的基于氨基酸手性的易于获得的、对映体选择性的Ru歧化催化剂的开发。这些催化剂将用于实现不对称闭环歧化反应(ARCM)，以形成不饱和杂环胺，这是制备天然产物的重要组成部分。为了说明这一方法，提出了一条快速组装抗菌剂(-)-西丹明的所有四个非对映异构体的对映选择性路线。此外，还将探索这类新型复分解催化剂中手性金属中心在控制烯烃交叉复分解反应中的E/Z非对映控制的作用。

DESCRIPTION (provided by applicant): Enantioselective and diastereoselective control in the synthesis of pharmacophores is now mandated due to the diversity of physiological properties exhibited by stereoisomers. Although olefin metathesis chemistry has undergone a renaissance in the development of ruthenium alkylidene catalysts, general stereochemical control remains a challenge. This proposal outlines the development of a new family of readily accessible, enantioselective ruthenium metathesis catalysts, based on amino acid chirality. These catalysts will be used to effect asymmetric ring closing metathesis (ARCM) to form unsaturated heterocyclic amines, important building blocks in the preparation of natural products. To illustrate this methodology, an enantioselective route for the rapid assembly of all four diastereomers of the antibiotic agent (-)-sedamine is proposed. Additionally, the effect of the chiral metal center in this new class of metathesis catalysts will be explored in controlling E/Z diastereocontrol in olefin cross-metathesis, an important application of metathesis in natural product synthesis.