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.本文报道了一种由有机嘧啶蝶啶（pyrimidopteridine）光氧化还原催化剂催化的光介导氢脱羧与氘脱羧反应，可适用于多种一级、二级及三级羧酸。本研究通过实验统计设计（Design of Experiment, DoE）对该反应进行了优化。在优化后的反应条件下，可实现以片剂形式商业化上市的非甾体抗炎药（Nonsteroidal Anti-inflammatory Drugs, NSAIDs）的克级规模转化。该反应的适用范围涵盖一级、二级及三级脂肪族生物活性羧酸。以廉价的重水（D₂O）作为氘源时，可实现最高95%的氘掺入率。本文还对反应敏感性评估以及用于阐明该反应机理的相关实验进行了讨论。