Synthesis of 2‐Aminopyridine Derivatives via a Tandem CuAAC/Ring‐Cleavage/[4+2]‐Cycloaddition/Rearrangement Reaction Sequence

Abstract

Abstract2H‐Azirines are an important class of small‐ring heterocycle that have been employed as versatile synthetic building blocks. Herein, a one‐pot CuAAC/ring‐cleavage/[4+2]‐cycloaddition/rearrangement reaction sequence involving terminal ynones, sulfonyl azides and 2H‐azirines is reported that leads to 2‐aminopyridine derivatives. In the first step, highly reactive N‐sulfonyl α‐acylketenimines are generated, via a CuAAC/ring‐cleavage process, from sulfonyl azides and terminal ynones and these undergo inverse electron‐demand Diels–Alder cycloaddition reactions with 2H‐azirines to form (isolable) 1,3‐oxazines that themselves undergo base‐promoted ring‐cleavage and rearrangement reactions to afford the title compounds.