Atom-economic generation of gold carbenes: gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles

Abstract

The generation of gold carbenes via the gold-catalyzed intermolecular reaction of nucleophiles containing relatively labile N–O or N–N bonds with alkynes has received considerable attention during recent years. However, this protocol is not atom-economic as the reaction produces a stoichiometric amount of pyridine or quinoline waste, the cleaved part of the N–O or N–N bonds. In this article, we disclose an unprecedented gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles, allowing rapid and practical access to a wide range of synthetically-useful 2-aminopyrroles. Most importantly, mechanistic studies and theoretical calculations revealed that this reaction presumably proceeds via an α-imino gold carbene pathway, thus providing a strategically novel, atom-economic route to the generation of gold carbenes. Other significant features of this approach include the use of readily-available starting materials, high flexibility, simple procedure, mild reaction conditions, and in particular, no need to exclude moisture or air (“open flask”).