Peripheral aryl group transposition on pyridines using photoredox catalysis

Installation of a functional group onto pyridines with predictable regiocontrol represents an appealing method for drug discovery programmes in the pharmaceutical industry. However, functionalization at the meta position of pyridines is often non-trivial owing to their inherent electronic properties, which commonly guide the reactions at the ortho and/or para positions. Here we report a method to enable regioselective migration of a peripheral aryl group on pyridines via 1,2-aryl migration of azacylohexadienyl radical intermediates generated by temporary dearomatization of the pyridine rings under photoredox catalysis. This process made it possible to transfer aryl substituents pre-installed at the para or ortho position of pyridines to the meta position by three different permutations: C4-to-C5, C4-to-C3 and C3-to-C2 aryl group transpositions. The present protocol exhibits broad functional group compatibility, offering streamlined access to a library of diverse meta-arylpyridines without the need for de novo synthesis. The meta-functionalization of pyridines is challenging owing to unfavourable electronic bias. Here a light-driven method to move aromatic functional groups on pyridines from the para or ortho position to the meta position is reported. This ‘peripheral editing’ strategy facilitates pyridine library construction by avoiding the need for de novo pyridine synthesis.