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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Published in | Angewandte Chemie International Edition Vol. 61; no. 51; p. e202212873 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
19.12.2022
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Subjects | |
Online Access | Get full text |
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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. |
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ISSN: | 1433-7851 1521-3773 |
DOI: | 10.1002/anie.202212873 |