Copper-catalyzed oxidative [2 + 2 + 1] cycloaddition: regioselective synthesis of 1,3-oxazoles from internal alkynes and nitriles

A robust and regioselective copper(II)-catalyzed cycloaddition of internal alkynes and nitriles providing an effective access to oxazole fragments is reported herein. Water substantially participated in this reaction. Control experiments proposed that this transformation may proceed via an enamide intermediate. This strategy enables the preparation of the core structure of a COX-2 inhibitor.