双金属协同催化立体发散性合成手性非天然α-氨基酸  

Stereodivergent synthesis of enantioenriched unnaturalα-amino acids enabled by synergistic dual metal catalysis

作　　者：卫亮 常鑫 张宗朋 汪昨非 王春江[1] Liang Wei;Xin Chang;Zongpeng Zhang;Zuo-Fei Wang;Chun-Jiang Wang(College of Chemistry and Molecular Sciences,Wuhan University,Wuhan 430072,China)

机构地区：[1]武汉大学化学与分子科学学院,武汉430072

出　　处：《科学通报》2023年第30期3956-3968,共13页Chinese Science Bulletin

基　　金：国家自然科学基金(22071186,22101216);湖北省自然科学基金(2020CFA036);中国博士后科学基金(2021M702514);中央高校基本科研业务费专项资金(2042022kf1180,2042022kf1040)资助。

摘　　要：手性非天然α-氨基酸是一类重要的化合物,在合成化学和生物医药领域都有十分广泛的应用.通过不对称催化合成高效构建手性非天然α-氨基酸,一直以来都是有机合成化学的研究热点之一,并且已经发展出多种较为成熟的合成途径.其中,最近几年兴起的双金属协同催化策略在该领域取得了巨大的成功.双金属协同催化在很多反应中表现出更高的催化活性,特别是可以通过催化剂的合理组合实现目标产物各种光学异构体的立体发散性精准合成,极大提升了该合成方法的高效与实用性,同时也为相关手性非天然α-氨基酸衍生物及其光学异构体的构效关系研究提供了便捷途径.本文对近年来双金属协同催化的立体发散性合成非天然氨基酸的研究进展进行了归纳,主要介绍该策略在亚甲胺叶立德参与的不对称烯丙基化和不对称炔丙基化反应中的应用,并讨论了相关局限性和发展前景.Enantioenriched unnaturalα-amino acids are one of the most important organic compounds which play a central role in both synthetic chemistry and pharmaceutical science.The catalytic asymmetric construction of unnaturalα-amino acids has been intensively investigated for decades with many efficient methodologies being established,such as asymmetric Strecker reaction,enantioselective hydrogenation of dehydroamino acids,and asymmetric Mannich or Mannich-type reactions of N-protectedα-iminoesters.Despite a variety of powerful catalytic systems showing high levels of reactivity and stereocontrol ability for amino acids synthesis,most of those methods can prepare only one of all possible stereoisomers through a chiral catalyst-controlled,thermodynamically or kinetically favored transition state.Metallated azomethine ylides are well-known as 1,3-dipoles,which have been widely employed in catalytic asymmetric 1,3-dipolar cycloaddition reactions to prepare enantioenriched N-heterocycles since the 1990s.In 2011,our group demonstrated the first example by leveraging metallated azomethines as nucleophiles in asymmetric Michael reaction,affordingα-amino acid derivatives in high yield and stereoselectivity.Since then,the catalytic asymmetricα-functionalization of metallated azomethine ylides attracted considerable attention and now is arguably one of the most straightforward and stereoselective methods for unnaturalα-amino acids.In particular,chiralα-amino acid synthesis from azomethine ylides enabled by synergistic dual metal catalysis has met with tremendous success in the past few years.This strategy involves the concurrent activation of two or more reactants by distinct catalysts,leading to the generation of corresponding more reactive species simultaneously in the reaction system,therefore can often exhibit superior catalytic reactivity than traditional mono-catalysis.Significantly,a pairwise combination of two distinct chiral metal catalysts build-up the potential of stereodivergent synthesis of the target compound

关 键 词：Α-氨基酸 双金属协同催化 立体发散性合成 不对称烯丙基化 不对称炔丙基化 

分 类 号：O621.251[理学—有机化学]