Copper-Catalyzed C(sp(3))-H/C(sp(3))-H Cross-Dehydrogenative Coupling with Internal Oxidants: Synthesis of 2-Trifluoromethyl-Substituted Dihydropyrrol-2-ols

摘要

The first oxidative C(sp(3))-H/C(sp(3))-H cross-dehydrogenative coupling (CDC) reaction promoted by an internal oxidant is reported. This copper-catalyzed CDC reaction of oxime acetates and trifluoromethyl ketones provides a simple and efficient approach towards 2-trifluoromethyldihydropyrrol-2-ol derivatives in a highly diastereoselective manner by cascade C(sp(3))-C(sp(3)) bond formation and cyclization. These products were further transformed into various significant and useful trifluoromethylated heterocyclic compounds, such as trifluoromethylated furan, thiophene, pyrrole, dihydropyridazine, and pyridazine derivatives. A trifluoromethylated analogue of an A beta(42) lowering agent was also synthesized smoothly. Preliminary mechanistic studies indicated that this reaction involves a copper(I)/copper(III) catalytic cycle with the oxime acetate acting as an internal oxidant.