不对称催化氢化反应研究

Study on Asymmetric Catalytic Hydrogenation Reactions

不对称催化氢化反应具有完美的原子经济性和清洁高效等特点,是最受青睐的不对称合成方法之一。虽然人们已经发展了很多用于不对称催化氢化的催化剂,但是这些催化剂往往存在稳定性差、活性低、底物适用范围窄、反应条件苛刻等问题,真正高效的手性催化剂很少。通过系统深入的研究,发展了30多个用于不对称氢化反应的原创性手性螺环催化剂,实现了潜手性酮、α-取代羰基化合物、不饱和羧酸、非保护烯胺等4大类20多种不对称氢化反应,反应的活性和对映选择性处于目前的最好水平,其中部分反应已经被用于手性药物及其中间体的生产,在国内外产生了重要影响。

The catalytic asymmetric hydrogenation, which features perfect atom-efficiency and clean and high effi- ciency, represents one of the most practical reactions in modern organic synthesis. Despite of tremendous efforts on the development of chiral catalysts, few have shown with both high reactivity and enantioselectivity to date. In this project, more than 30 chiral catalysts were developed and successfully applied in enantioselective hydrogenation re- actions of prochiral ketones, a-substituted carbonyl compounds, unsaturated acids, and unprotected enamines. These asymmetric hydrogenation reactions showed high activity and enantioselectivity, and some of them have been successfully applied in scaled-up synthesis of chiral drugs or key intermediates.