Thioxanthone modified flavin for photo-decarboxylation of aromatic acids to enable C-2 arylation of nitrogen heterocycles

Abstract

Visible-light-induced decarboxylation of aryl carboxylic acids has become a promising for the generation of aryl radical precursors. Due to the inherent limitations of traditional photosensitizers, the application of this strategy in organic synthesis is restricted. To overcome this limitation, a binary photocatalyst thioxanthone modified flavin (TX-Flavin) was designed and synthesized based on the photocatalytic decarboxylation ability of flavin and the excellent reaction performance of thioxanthone (TX) under light. A series of photoelectric performance tests showed that the stability and catalytic performance of photocatalysts under high-energy light sources have been significantly improved by combining TX with flavin structure. TX-Flavin was used as a photocatalyst for decarboxylation of aryl carboxylic acids to develop C-2 arylation of imidazo[1,2-a]pyridine and N-acetylbenzimidazole, and a series of 2-aryl-N-heterocyclic compounds were obtained in good yields. Meanwhile, by combining density functional theory (DFT) calculations, the Gibbs free energy changes of key intermediates in the proposed catalytic cycle were analyzed, further confirming the rationality of the reaction mechanism.Besides, this method provides a new strategy for the synthesis of the anti-ulcer drug Zolimidine, which further demonstrate the practicability of this protocol. At the same time, the reaction conditions of no metal, no pre activation of aryl carboxylic acids, and high functional group tolerance provide new ideas for the decarboxylation strategy of aryl carboxylic acids and the design of photocatalysts.