Photocatalytic Decarboxylative Pyridylation of Carboxylic Acids Using In Situ-Generated Amidyl Radicals as Oxidants

Site-selective C-H functionalization of heteroarenes is important for the rapid modification of bioactive molecules. Herein, we report an efficient photocatalytic platform for the visible-light-mediated C-H alkylation of pyridines at the C4 position using alkyl carboxylic acids as alkylating agents under external oxidant-free conditions. Importantly, the released N-centered radical can serve as an effective oxidizing agent for single-electron transfer (SET) oxidation to efficiently regenerate the photocatalyst. This photocatalytic system is appealing from a mechanistic perspective and is amenable to a broad substrate scope for carboxylic acids and pyridines containing oxidatively sensitive functionalities that do not hold up to other procedures. The strategy offers a practical approach for the C4-selective pyridylation of a diverse range of primary, secondary, and tertiary carboxylic acids and amino acids with various functional groups under mild, metal-free conditions.

Automated summary

A highly efficient visible-light-mediated C-H alkylation of pyridines at the C4 position using alkyl carboxylic acids as alkylating agents is reported in this study. The released N-centered radical acts as an effective oxidizing agent for single-electron transfer (SET) oxidation to regenerate the photocatalyst, making this photocatalytic system appealing from a mechanistic perspective. The strategy offers a practical approach for the C4-selective pyridylation of carboxylic acids and amino acids with various functional groups under mild, metal-free conditions.