Photocatalyzed Generation of Acyl Radicals from Aryl/Alkyl Acyl Halides via Nucleophilic Substitution

Abstract

Herein, we introduce a nucleophilic catalysis strategy based on 1methylpyridine-2(1H)-thione (MPT) catalyst, which mediates the in-situ generation of photoactive intermediates from various acyl halides. This strategy enables efficient formation of both aryl and alkyl acyl radicals upon visible-light irradiation, including those derived from otherwise unreactive alkyl acyl fluorides/chlorides.Acyl halides are inexpensive, abundant, highly reactive, and commercially available chemicals that have been extensively employed in organic synthesis, 1, 2 traditionally engaging in transformations via acyl cation intermediates. Concurrently, visible-light photoredox catalysis has emerged as a powerful, sustainable, and environmentally benign synthetic strategy. [3][4][5] This strategy has unlocked diverse acyl radical precursors, including ketoacids, aldehydes, and notably, acyl chlorides, thereby significantly expanding the synthetic toolbox for radical acylation reactions with high synthetic potential.Through the photooxidative pathways, ketoacids have been established as versatile aryl and alkyl acyl sources, enabling efficient construction of C-C 6-9 and C-X 10 bonds. Aldehydes are also used as acyl radical sources via photoinduced hydrogen atom transfer process, participating in radical addition reactions 11,12 , coupling reactions 13 and functional group conversion reactions 14,15 . Through the photoreductive pathway, acid anhydride 16 and acid chloride [17][18][19][20] have been utilized for acyl radical generation, though the latter have been limited to aryl acid chlorides. Additional methods, such as the phosphorus-mediated deoxygenation of carboxylic acids [21][22][23] , along with thioester [24][25][26] and acyl silanes 27 , further complement the toolbox for acyl radical generation.However, the photocatalytic application of carboxylic acid derivatives, particularly alkyl acyl halides and acid anhydrides, remains constrained by redox potential limitations 28-30 (Scheme 1a). For instance, acetyl chloride (E1/2 red = -1.98 V 29 vs SCE.) and c) MPT catalyzed acyl radical formation via nucleophilic substitution (this work)