Asymmetric [3+2] Annulations to Construct 1,2-Bispirooxindoles Incorporating a Dihydropyrrolidine Motif

Constructing chiral bispirooxindoles is difficult to achieve but highly attractive owing to their many potential applications in medicinal chemistry. Here we present an asymmetric [3+2] annulation reaction of Morita-Baylis-Hillman carbonates from isatins and isatin-based N-Boc-ketimines under the catalysis of a newly designed multifunctional 4-dimethylaminopyridine-type substance. The reaction shows high gamma-regioselectivity, producing highly complex 1,2-bispirooxindoles incorporating a dihydropyrrolidine motif in excellent yields with moderate to outstanding stereoselectivity (dr > 19: 1, up to > 99% ee). This protocol has been expanded to utilize trifluoromethyl-containing ketimines, delivering complicated architectures with fused and spirocyclic frameworks in modest enantioselectivity.