Photomediated Hydro- and Deuterodecarboxylation of Pharmaceutically Relevant and Natural Aliphatic Carboxylic Acids

Herein, we report a photomediated hydro- and deuterodecarboxylation of different primary, secondary, and tertiary carboxylic acids catalyzed by an organic pyrimidopteridine photoredox catalyst. The reaction was optimized by a statistical design of experiment (DoE). Under optimized reaction conditions, the conversion of commercially available nonsteroidal anti-inflammatory drugs (NSAIDs) in tablet form and on gram scale was realized. The scope of the application comprises primary, secondary, and tertiary aliphatic biologically active carboxylic acids. A deuterium incorporation of up to 95% by using D2O as inexpensive deuterium source was achieved. A sensitivity assessment as well as experiments aiding the elucidation of the reaction mechanism are discussed.

Automated summary

In this study, we demonstrate a photomediated hydro- and deuterodecarboxylation of carboxylic acids using an organic pyrimidopteridine photoredox catalyst. The reaction was optimized using a statistical design of experiment and successfully converted NSAID tablets and larger quantities. This method can be applied to primary, secondary, and tertiary aliphatic biologically active carboxylic acids with high deuterium incorporation.