Decarboxylative Arylation and Alkoxylation of Pyridine-2carboxylic acid N-oxide derivatives via Electrophilic Carbene: Access to Lucidimine E and Australine

Abstract

Herein, we report a direct decarboxylative functionalization of pyridine-2-carboxylic acid N-oxide derivatives via N-trifluoroacetoxy carbene intermediate utilizing trifluoroacetic anhydride as an alternative to transition-metal catalysts and organometallic reagents. This general and robust synthetic method enables preparation of various 2-aryl, 2-heteroaryl, and 2-alkoxy pyridine derivatives, demonstrating a broad substrate scope and compatibility with diverse functional groups. Additionally, this approach has been successfully employed in the first total synthesis of the bioactive natural alkaloids Lucidimine E and Australine.