Skip to main content

Research Repository

Advanced Search

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

Ruffell, Katie; Gallegos, Liliana; Ling, Kenneth; Paton, Robert S.; Ball, Liam T.


Katie Ruffell

Liliana Gallegos

Kenneth Ling

Robert S. Paton

Associate Professor


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.


Ruffell, K., Gallegos, L., Ling, K., Paton, R. S., & Ball, L. T. (2022). Umpolung Synthesis of Pyridyl Ethers by Bi(V)‐Mediated O‑Arylation of Pyridones. Angewandte Chemie International Edition, 61(51), Article e202212873.

Journal Article Type Article
Acceptance Date Oct 17, 2022
Online Publication Date Nov 17, 2022
Publication Date Dec 19, 2022
Deposit Date Oct 27, 2022
Publicly Available Date Nov 2, 2022
Journal Angewandte Chemie - International Edition
Print ISSN 1433-7851
Electronic ISSN 1521-3773
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 61
Issue 51
Article Number e202212873
Public URL
Publisher URL


You might also like

Downloadable Citations