Copper-Catalyzed Umpolung Strategy of N-2,2,2-Trifluoroethylisa-tin Ketimines for the Synthesis of Spirobenzodiazepine Oxindoles.

A copper-catalyzed umpolung [4+3] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with ethynyl benzoxazinanones is reported, featuring rare Cα-selective nucleophilic reactivity of the ketimine (overcoming the typical predominance of Cα'-position). This protocol affords 1,3-benzodiazepines embedded with a spirooxindole scaffold in high yields and excellent diastereoselectivities, with broad substrate scope and good functional group tolerance. The products integrate pharmacophoric 1,3-benzodiazepine, spirooxindole, and trifluoromethyl moieties, holding promise for drug discovery.