Brønsted Base-Catalyzed Formal Reductive [3+2] Annulation of 4,4,4-Trifluorocrotonate and α-Iminoketones

A formal reductive [3+2] annulation of 4,4,4-trifluorocrotonate and α-iminoketones was developed under Brønsted base catalysis. A single phosphazene base efficiently catalyzes the one-pot tandem reaction involving two mechanistically different elementary processes, namely the chemoselective reduction of an imine moiety of α-iminoketones with thiols as the reductant and the subsequent intermolecular Michael addition of an enolate of α-aminoketones concomitant with lactam formation. This operationally simple method provides β-trifluoromethyl-substituted γ-lactams with a tetrasubstituted carbon as a single diastereomer.