Synthesis of 2,4,5-Trisubstituted Oxazoles from Copper-Mediated Benzylic sp3 C-H Aerobic Oxidative Annulation of Ketones and Amines via a Cascade Reaction

The functionalization of sp(3) carbons is deemed challenging in synthetic organic chemistry yet has tremendous potential in producing potent organic compounds. A facile synthesis of 2,4,5-trisubstituted oxazoles through an oxidative, copper-catalyzed, and solvent-free annulation is described. Various arylated oxazoles were efficaciously synthesized at a mild temperature from readily available substrates under a molecular oxygen atmosphere. Preliminary mechanistic studies suggested that the reaction proceeds via an anionic-type mechanism and indicated the formation of a keto-imine intermediate. The reaction is notable for the abstraction of six hydrogen atoms, the functionalization of one sp(2) carbon and two sp(3) carbons, and the formation of C-O and C-N bonds.