Transition-Metal-Free Regioselective Direct C2, C4 Difunctionalization and C2, C4, C6 Trifunctionalization of Pyridines

This study reports the invention of di- or trifunctionalization of readily available pyridines (including all the pyridine substrates utilized in this paper, such as 3-cyanopyridine and 3-chloropyridine) through dearomative functionalization-oxidative rearomatization under transition-metal- and reductant-free conditions. Although a two-step operation is required, the crude product of the first step could be used in the next step directly. Typically, 3-pi-EWG pyridines undergo difunctionalization, whereas 3-sigma-EWG pyridines participate in trifunctionalization, affording multisubstituted piperidines. Computational studies provide detailed insights for their distinct reactivity in the title reaction.