Homochiral α-amino acids are widely used in pharmaceutical design as key subunits in chiral catalyst synthesis or as building blocks in synthetic biology. Many synthetic methods have been developed to access rare or unnatural variants by controlling the installation of the α-stereocentre. By contrast, and despite their importance, α-amino acids possessing β-stereocentres are much harder to synthesize. Here we demonstrate an iridium-catalysed protocol that allows the direct upconversion of simple alkenes and glycine derivatives to give β-substituted α-amino acids with exceptional levels of regio- and stereocontrol. Our method exploits the native directing ability of a glycine-derived N–H unit to facilitate Ir-catalysed enolization of the adjacent carbonyl. The resulting stereodefined enolate cross-couples with a styrene or α-olefin to install two contiguous stereocentres. The process offers very high levels of regio- and stereocontrol and occurs with complete atom economy. In broader terms, our reaction design offers a unique directing-group-controlled strategy for the direct stereocontrolled α-alkylation of carbonyl compounds, and provides a powerful approach for the synthesis of challenging contiguous stereocentres.

同手性 α-氨基酸作为手性催化剂合成的关键亚基或合成生物学的构建模块广泛应用于药物设计。已经开发出许多合成方法来通过控制 α-立体中心的安装来获得罕见或非自然的变体。相比之下，尽管具有 β-立构中心的 α-氨基酸很重要，但其合成却要困难得多。在这里，我们展示了一种铱催化的方案，该方案允许简单烯烃和甘氨酸衍生物的直接上转换，以产生具有特殊水平的区域和立体控制的β-取代的α-氨基酸。我们的方法利用甘氨酸衍生的 N-H 单元的天然定向能力来促进相邻羰基的 Ir 催化烯醇化。所得立体定义的烯醇化物与苯乙烯或α-烯烃交叉偶联以安装两个连续的立构中心。该过程提供了非常高水平的区域和立体控制，并且具有完全的原子经济性。从更广泛的角度来看，我们的反应设计为羰基化合物的直接立体控制α-烷基化提供了独特的定向基团控制策略，并为合成具有挑战性的连续立构中心提供了强大的方法。