Synthesis of Enantiomerically Pure 2,2,3,4,5-Pentasubstituted Pyrrolidines by Phenylsulfanyl Migration

Enantiomerically pure 2,2,3,4,5-pentasubstituted pyrrolidines can be prepared, in high overall yield, from α,β-unsaturated esters. Asymmetry is introduced via a Michael addition, and additional stereogenic centers are introduced by an aldol reaction. A novel stereospecific ring-forming reaction, proceeding via a thiiranium (episulfonium) ion, yields pyrrolidines from β-hydroxy sulfides. In this manner, 2,2,3,4,5-pentasubstituted pyrrolidines, containing three contiguous stereogenic centers around the ring, can be prepared in 44% overall yield from ethyl crotonate.