Nickel-Catalyzed Asymmetric Homobenzylic Hydroamidation of Vinylarenes: A Strategy for Chiral β-(Hetero)arylethylamides

Herein, we introduce a Ni-catalyzed asymmetric homobenzylic hydroamidation reaction that efficiently addresses the dual challenge of achieving regio- and enantioselectivity in the synthesis of β-(hetero)arylethylamides. By employing a transposed NiH catalysis approach, this method facilitates the formation of key nickel-amido intermediates, enabling migratory insertion into alkenes to produce the desired products. The reaction exhibits excellent functional group tolerance and utilizes simple, readily available starting materials, thereby readily accessing pharmaceutical and natural product frameworks. Notably, the approach was applied to the synthesis of pharmaceutical compounds and natural products, such as Sacubitril and Cipargamin, showcasing its potential to streamline the process with high yields and selectivity. This work underscores the transformative role of NiH catalysis in expanding the toolbox of asymmetric hydroamidation.