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

• Published in: Chemical science (Cambridge) 2015-01, Vol.6 (2), p.1265-1271
• Main Authors: Zhou, Ai-Hua, He, Qiao, Shu, Chao, Yu, Yong-Fei, Liu, Shuang, Zhao, Tian, Zhang, Wei, Lu, Xin, Ye, Long-Wu
• Format: Article
• Language: English
• Subjects: Alkynes; Carbenes; Cycloaddition; Flexibility; Gold; Mathematical analysis; Nucleophiles; Quinoline
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c4sc02596b

The generation of gold carbenes 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 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").