α-Amino acids are essential for life as building blocks of proteins and components of diverse natural molecules. In both industry and academia, the incorporation of unnatural amino acids is often desirable for modulating chemical, physical and pharmaceutical properties. Here we report a protocol for the economical and practical synthesis of optically active α-amino acids based on an unprecedented stereocontrolled 1,3-nitrogen shift. Our method employs abundant and easily accessible carboxylic acids as starting materials, which are first connected to a nitrogenation reagent, followed by a highly regio- and enantioselective ruthenium- or iron-catalysed C(sp³)–H amination. This straightforward method displays a very broad scope, providing rapid access to optically active α-amino acids with aryl, allyl, propargyl and alkyl side chains, and also permits stereocontrolled late-stage amination of carboxylic-acid-containing drugs and natural products.

α-氨基酸作为蛋白质的组成部分和多种天然分子的组成部分对生命至关重要。在工业界和学术界，为了调节化学、物理和药物特性，通常需要加入非天然氨基酸。在这里，我们报告了一种基于前所未有的立体控制 1,3-氮位移的光学活性 α-氨基酸的经济实用合成方案。我们的方法采用丰富且易于获得的羧酸作为起始材料，首先连接到氮化试剂，然后连接到高度区域和对映选择性的钌或铁催化的 C( sp ³)–H 胺化。这种简单的方法显示了非常广泛的范围，可以快速获得具有芳基、烯丙基、炔丙基和烷基侧链的光学活性 α-氨基酸，并且还允许对含羧酸的药物和天然产物进行立体控制的后期胺化。