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

Abstract

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.

Visible-Light Photoredox-Catalyzed Decarboxylation of α-Oxo Carboxylic Acids to C1-Deuterated Aldehydes and Aldehydes

“…Notably, α-oxocarboxylic acids have proven to be good precursors for acyl radical by decarboxylation via visible-light photoredox catalysis, and the synthesis of C1-deuterated aldehydes using α-oxocarboxylic acid via acyl radical under visible-light irradiation has not been explored. Inspired by visible-light photoredox-catalyzed transformation of carboxylic acid group, especially in decarboxylation of alkyl carboxylic acid, ,,,, herein, we report decarboxylation of α-oxo carboxylic acids for C1-deuterated aldehydes via carboxyl radical and acyl radical under visible-light irradiation at ambient temperature with D 2 O as the deuterium source (Scheme c). Diverse C1-deuterated aldehydes were achieved in up to 92% yields and 91–97% D incorporation.…”