Nucleophilic Phosphine-Catalyzed Intramolecular Michael Reactions of <i>N</i>-Allylic Substituted α-Amino Nitriles: Construction of Functionalized Pyrrolidine Rings via 5-<i>endo</i>-trig Cyclizations

Abstract

Pyrrolidine rings are common moieties for pharmaceutical candidates and natural compounds, and the construction of these skeletons has received much attention. α-Amino nitriles are versatile intermediates in synthetic chemistry and have been widely used in the generation of multiple polyfunctional structures. Herein, a novel nucleophilic phosphine-catalyzed intramolecular Michael reaction of N-allylic substituted α-amino nitriles has been developed for the efficient construction of functionalized 2,4-disubstituted pyrrolidines (N-heterocyclic α-amino nitriles) via 5-endo-trig cyclization. Furthermore, the one-pot sequence of the synthesis of pyrrolidine and the subsequent transformations of the functionalized products have also been demonstrated.