Umpolung Synthesis of Pyridyl Ethers by Bi(V)‐Mediated O‐Arylation of Pyridones

We report that O‐selective arylation of 2‐ and 4‐pyridones with arylboronic acids is affected by a modular, bismacycle‐based system. The utility of this umpolung approach to pyridyl ethers, which is complementary to conventional methods based on S(N)Ar or cross‐coupling, is demonstrated through the concise synthesis of Ki6783 and picolinafen, and the formal synthesis of cabozantib and golvatinib. Computational investigations reveal that arylation proceeds in a concerted fashion via a 5‐membered transition state. The kinetically‐controlled regioselectivity for O‐arylation—which is reversed relative to previous Bi(V)‐mediated pyridone arylations—is attributed primarily to the geometric constraints imposed by the bismacyclic scaffold.