Palladium-Catalyzed Meta-Selective Suzuki Coupling of 3,4-Dichloropyridine through N -Oxidation/Deoxygenation

The site-selective coupling of polyhalogenated heteroarenes remains a persistent and significant hurdle in synthetic chemistry. Compared with the well-established ortho- and para-selective couplings of dichloropyridine, the meta-selective coupling of dichloropyridine has not been developed until now. Herein, we report an electronic modulation strategy for the palladium-catalyzed meta-selective Suzuki coupling of 3,4-dichloropyridine through N -oxidation/deoxygenation. Density functional theory (DFT) calculations reveal that N -oxide modifies both bond dissociation energies (BDEs) and transition-state barriers, providing a clear mechanistic rationale for this reversal in site selectivity from para-selectivity of pyridine to meta-selectivity of its N -oxide. This work establishes N -oxide-directed electronic modulation as a versatile and complementary method for the modular construction of privileged arylpyridines.