Chiral Brønsted Base Activation of Donor–Acceptor Cyclopropanes toward Diastereo- and Enantioselective 3 + 2 Cycloaddition with Isatin-Derived Ketimines

Organocatalyzed diastereo- and enantioselective 3 + 2 cycloaddition reactions of donor-acceptor (D-A) cyclopropanes with isatin-derived ketimines are presented. Different from well-developed Lewis acid activation protocols which promote the reactivity of D-A cyclopropanes through coordinating to the acceptor group, in this reaction, dicyanocyclopropylmethyl ketones can be activated through nucleophilic activation of the donor group by using dihydroquinine-derived squaramide as Brønsted base catalyst. The reaction affords functionalized spirooxindole-3,2'-pyrrolidines with two nonadjacent tetra- and tri-substituted stereocenters in 83-99% yields, moderate to excellent diastereoselectivities (up to >20:1 diastereomeric ratio (dr)), and excellent enantioselectivities (up to >99% enantiomeric excess (ee)) under mild conditions.