Zincke-Imine-Based Peripheral Editing of 2-Arylpyridines to Access 3-Acylpyridines

Skeletal and peripheral editing of pyridines is a powerful strategy for the late-stage functionalization of N-heterocycles. While pyridines inherently exhibit high reactivity at the C2 and C4 positions, functionalization at the C3 position is significantly more challenging and less explored. Herein, we report a distinct dearomatization-rearomatization strategy that transforms 2-substituted pyridines into synthetically challenging 3-acylpyridines in good to excellent yields via an unprecedented rearrangement of a Zincke imine. Notably, an operationally simple one-pot variant circumvents the need to isolate Zincke imines, a bottleneck in related methodologies. In contrast to traditional electrophilic acylation, our strategy proceeds under mild conditions and exhibits high selectivity for the electron-deficient triene fragment.