An Efficient [2 + 2 + 1] Synthesis of 2,5-Disubstituted Oxazoles via Gold-Catalyzed Intermolecular Alkyne Oxidation

Abstract

The first efficient intermolecular reaction of gold carbene intermediates generated via gold-catalyzed alkyne oxidation has been realized using nitriles as both the reacting partner and the reaction solvent, offering a generally efficient synthesis of 2,5-disubstituted oxazoles with broad substrate scope. The overall reaction is a [2 + 2 + 1] annulation of a terminal alkyne, a nitrile, and an oxygen atom from an oxidant. The reaction conditions are exceptionally mild, and a range of functional groups are easily tolerated. With complex and/or expensive nitriles, only 3 equiv could be sufficient to achieve serviceable yields in the absence of any solvent and using only 1 mol % BrettPhosAuNTf(2) as the catalyst.