过渡金属催化的不对称卡宾插入反应在手性胺合成中的应用

Transition metal-catalyzed asymmetric carbene insertion for synthesis of chiral amines

手性胺是一类重要的化合物,在合成化学和生物医药领域都有着广泛的应用.近20年来,伴随着过渡金属催化不对称合成研究的发展,高效高选择性合成手性胺的方法越来越多.其中,过渡金属催化的不对称卡宾插入反应已经成为合成各种手性胺,尤其是非天然手性氨基酸的一种最为有用的方法.近年来,以铜、铑、钯为代表的过渡金属卡宾对芳香胺、酰胺、咔唑、亚胺等底物的不对称N-H插入反应研究已经取得了积极的进展,最近对脂肪胺类底物也取得了重大突破.这些结果为结构多样的手性胺合成提供了重要方法,也为过渡金属催化下芳香胺、脂肪胺的不对称转化提供了新的思路.本文对近年来过渡金属催化的不对称卡宾插入反应的研究进展进行了归纳,主要介绍金属卡宾对各种胺类底物的不对称N-H插入反应在手性胺合成中的应用.

Chiral amines are an important class of organic compounds. They are ubiquitous in organic chemistry and often serve as fundamental building blocks, versatile synthons, efficient chiral catalysts, ligands or auxiliaries in asymmetric synthesis and medicinal chemistry. During the past few decades, there has been remarkable progress in the development of efficient asymmetric methods. Accordingly, asymmetric synthesis, particularly catalytic enantioselective synthesis of chiral amines has received considerable attention from both academia and industry. Among them, transition metal-catalyzed asymmetric carbene insertion has emerged as one of the most useful and powerful methods for synthesis of various chiral amines through the efficient construction of the C-N bonds. In this review, we present the progress and advances that have been made using copper, rhodium, palladium, and iron catalysts to perform enantioselective N-H insertion reactions with diazo compounds. An overview of early examples of Cu(I) and Ag(I)-bisoxazoline-catalyzed asymmetric N-H insertion and the subsequent developments by using copper(I) complexes with chiral spiro bisoxazolines, bipyridines and binol derivatives,as well as with rhodium(II)-, palladium(II)-, iron(II)-carbene chemistry is provided. In these work, catalytic asymmetric metal-carbene insertion into the N-H bond of aromatic amines, amides(Boc NH2, Cbz NH2), substituted carbazoles and indoles, and benzophenone imines were achieved under mild reaction conditions, allowing access to a wide variety of structurally important chiral amines in enantiomerically enriched form. In particular, with the use of α-aryl or α-alkyl α-diazoesters as carbene precusors, both aryl and alkyl substituted α-amino esters could be prepared in good yields with high enantioselectivities. A recent major breakthrough in enantioselective transition-metal-catalyzed N-H insertion reactions with aliphatic amines is also discussed. By using a combination of an achiral copper complex and chiral amino-thiourea catalyst, highly enantioselective carbene insertion into N-H bonds of aliphatic amines was achieved to produce various chiral α-alkyl α-amino acid derivatives bearing secondary and tertiary amino substituents in good yields. Overall, this review summarizes the most prominent work on transition-metal-catalyzed asymmetric carbene N-H insertion and their applications in chiral amines and natural or unnatural chiral α-amino acid derivatives synthesis.