Synthesis of 2,4,5-Trisubstituted Oxazoles from Copper-Mediated Benzylic sp<sup>3</sup> C–H Aerobic Oxidative Annulation of Ketones and Amines via a Cascade Reaction
Mncedisi Mazibuko, Vineet Jeena
Abstract
The functionalization of sp3 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 sp2 carbon and two sp3 carbons, and the formation of C–O and C–N bonds.