Predictably selective (sp3)C-O bond formation through copper catalyzed dehydrogenative coupling: Facile synthesis of dihydro-oxazinone derivatives

Abstract

An intramolecular dehydrogenative (sp3)C-O bond formation in salicylamides can be initiated by an active Cu/O2 species to generate pharamaceutically relevant dihydro-oxazinones. Experimental findings suggest that stereoelectronic parameters in both coupling partners are controlling factors for site selectivity in bond formation. Mechanistic investigations including isotope labeling, kinetic studies helped to propose a catalytic cycle. The method provides a convenient synthesis of an investigational new medicine CX-614, which has potential in finding treatment for Parkinson's and Alzheimer's diseases. © 2014 American Chemical Society.