A Versatile Method for the Facile Synthesis of Enantiopure trans- and cis-2,5-Disubstituted Pyrrolidines

Treatment of (2S)-1-O-benzylglycerol-2,3-bistriflate (2) with the trilithiated species of chiral building blocks 5−7 provided 2,3,5-trisubstituted pyrrolidines that were subjected to reductive desulfonylation to give trans-2,5-disubstituted pyrrolidines 11−13, respectively. The same reaction sequence with the (2R)-bistriflate 4 and trilithiated 5 afforded the cis isomer 19. This two-step synthetic mehodology can furnish any one of the four possible diastereomers of enantiopure 2,5-disubstituted pyrrolidines in 60−72% overall yields.