美国加州大学伯克利分校John F. Hartwig研究团队的一项最新研究，找到了将胺中N-H键不对称加成到内烯烃上的催化体系，相关论文发表在2020年11月3日的《自然》杂志上。

该课题组人员报道了一个阳离子含铱体系，用于催化包括环内和直链烯烃在内的一系列未活化内烯烃发生分子间加氢胺化反应，产生高光学选择性的手性胺。这种催化剂包含一种新的配体和三氟甲磺酸胺反离子，并在反应设计中加入了2-氨基-6-甲基吡啶，作为氨替代物的同时在催化循环中促进多个步骤的反应速率。这些设计原理为在未活化内烯烃上加成N-H、O-H或C-H键指明了道路，大大简化了从基本化学原料合成功能分子的过程。

加氢胺化反应，即胺中N-H键在烯烃上的加成反应，是一个基础但有挑战性的有机反应，该反应可在100%原子经济性下，利用两种来源充足的化学原料——烯烃和胺——生成烷基胺。这个反应尤为重要，因为胺（尤其是手性胺）是许多天然产物和药物中常见的基团。虽然已有许多发展加氢胺化反应催化剂的努力，绝大多数发生分子间加氢胺化反应的烯烃还局限于共轭、具有环张力的或末端的烯烃；只有少数几个案例中胺上的N-H键可以直接加成在未活化内烯烃上，包括最近报道的光催化加氢胺化，但发生在未活化内烯烃上的分子间手性加成尚未见诸报道。

事实上，在这篇报道之前，所有不使用导向基团、在任何未活化烯烃上直接发生的分子间手性加氢胺化反应，只能获得很一般的光学选择性。

附：英文原文

Title: Catalytic asymmetric addition of an amine N–H bond across internal alkenes

Author: Yumeng Xi, Senjie Ma, John F. Hartwig

Issue&Volume: 2020-11-03

Abstract: Hydroamination of alkenes, the addition of the N–H bond of an amine across an alkene, is a fundamental, yet challenging, organic transformation that creates an alkylamine from two abundant chemical feedstocks, alkenes and amines, with full atom economy. The reaction is particularly important because amines, especially chiral amines, are prevalent substructures in a wide range of natural products and drugs. Although extensive efforts have been dedicated to developing catalysts for hydroamination, the vast majority of the alkenes that undergo intermolecular hydroamination have been limited to conjugated, strained, or terminal alkenes;only a few examples occur by the direct addition of the N–H bond of amines across unactivated internal alkenes, including recent photocatalytic hydroamination, and enantioselective intermolecular additions to such alkenes are not known. In fact, current examples of direct, enantioselective intermolecular hydroamination of any type of unactivated alkene lacking a directing group occur with only moderate enantioselectivity. Here we report a cationic iridium system that catalyses intermolecular hydroamination of a range of unactivated, internal alkenes, including those in both acyclic and cyclic alkenes, to afford chiral amines with high enantioselectivity. The catalyst contains a new ligand and triflimide counteranion, and the reaction design includes 2-amino-6-methylpyridine as the amine to enhance the rates of multiple steps within the catalytic cycle while serving as an ammonia surrogate. These design principles point the way to the additions of N–H bonds of other reagents, as well as O–H and C–H bonds, across unactivated internal alkenes to streamline the synthesis of functional molecules from basic feedstocks.

DOI: 10.1038/s41586-020-2919-z

Source: https://www.nature.com/articles/s41586-020-2919-z