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 Ar or cross-coupling, is demonstrated through the co...

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Bibliographic Details
Published inAngewandte Chemie International Edition Vol. 61; no. 51; p. e202212873
Main Authors Ruffell, Katie, Gallegos, Liliana C, Ling, Kenneth B, Paton, Robert S, Ball, Liam T
Format Journal Article
LanguageEnglish
Published Germany 19.12.2022
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Summary: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 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 -mediated pyridone arylations-is attributed primarily to the geometric constraints imposed by the bismacyclic scaffold.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202212873