Site-Selective C-H Acylation of Pyridinium Derivatives by Photoredox Catalysis

A strategy for visible-light-induced site-selective C-H acylation of pyridinium salts was developed by employing N-methoxy- or N-aminopyridinium salts, offering a powerful synthetic tool for accessing highly valuable C2- and C4-acylated pyridines. The methoxy or amidyl radicals photocatalytically generated from the pyridinium salts can undergo hydrogen atom abstraction from readily available aldehydes to form acyl radicals, which can engage in addition to pyridinium substrates. Remarkably, the use of N-methoxypyridinium salts preferentially gives the C2-acylated pyridines, and the site selectivity can be switched from C2 to C4 by using N-aminopyridinium salts. The utility of this transformation was further demonstrated by the late-stage functionalization of complex biorelevant molecules and by application of acyl radicals to photocatalytic radical cascades.