Combined Photoredox and Carbene Catalysis for the Synthesis of α-Amino Ketones from Carboxylic Acids

alpha-Amino ketone moieties are present in many pharmacologically active molecules, but their synthesis is challenging. Herein, we report a mild, operationally simple method for direct acylation of alpha-amino C(sp(3))-H bonds from carboxylic acids via the merger of carbene and photoredox catalysis. Specifically, cross-coupling reactions between a wide range of carboxylic acids, a class of feedstock chemicals, and readily available N-alkyl anilines by means of single-electron N-heterocyclic carbene catalysis combined with photocatalysis provided access to structurally diverse alpha-amino ketones. The method features a broad substrate scope and is compatible with a wide array of functional groups. To demonstrate the potential applications of the method, we subjected one of the alpha-amino ketone products to further transformations.

Automated summary

We report a mild and operationally simple method for the direct acylation of α-amino C(sp(3))-H bonds from carboxylic acids. The method combines carbene and photoredox catalysis and successfully synthesizes structurally diverse α-amino ketones through the cross-coupling reactions between a wide range of carboxylic acids and readily available N-alkyl anilines. This method demonstrates a broad substrate scope and compatibility with various functional groups.