Exploration of the Copper-Catalyzed Sydnone and Sydnonimine-Alkyne Cycloaddition Reactions by High-Throughput Experimentation

Abstract

The reactivity of sydnones and sydnonimines toward terminal alkynes under copper catalysis has been explored using High-Throughput-Experimentation. A large panel of ligands and reaction conditions have been tested to optimize the copper-catalyzed sydnone click reaction discovered by our group ten years ago. This screening approach led to the identification of new ligands, which boosted the catalytic properties of copper and allowed the discovery of a new copper-catalyzed click-and-release reaction involving sydnonimines. This reaction allowed chemoselective ligation of terminal alkynes with sydnonimines and, simultaneously, the release of an isocyanate fragment molecule that can be used for further transformations.

Keywords: Copper; Cycloaddition; Mesoionics; Screening; Sydnones.