Synthesis of α-trifluoromethyl-β-lactams via a copper-catalyzed Kinugasa reaction of nitrones with 3,3,3-trifluoropropyne and their defluorination

Abstract

An efficient protocol for synthesizing α-trifluoromethyl-β-lactams through a copper-catalyzed Kinugasa reaction of nitrones with in situ generated 3,3,3-trifluoropropyne is reported. The reaction proceeds through the generation of the Cu(I) acetylide species, followed by a regioselective [3 + 2] cycloaddition sequence with rearrangement and elimination to construct substituted α-trifluoromethyl-β-lactam products in moderate to good yields. Aside from gram-scale synthesis, the prepared compounds were evaluated for late-stage functionalization including defluorination.