Umpolung (4 + 1) Annulations of Bifunctional Hydroxylamines: A Modular Approach to Pyrrolidines

Herein we describe a modular and umpolung (4 + 1) cyclization strategy for synthesizing functionalized 2,2-disubstituted pyrrolidines decorated with versatile alkene, alkyne, and carbonyl groups under mild basic conditions. The new approach employs readily accessible N-haloalkyl hydroxylamines as distinctive carbon-nitrogen bielectrophiles, enabling a tandem C-C alkylation and umpolung C-N ring-closing reaction with diverse carbonyl nucleophiles. Furthermore, a catalytic asymmetric variant of this reaction has been also achieved with moderate enantioselectivity (72% ee) under the chiral phase-transfer catalytic conditions.