New diastereoselective route to 2-substituted cis-(2S,5S)- and trans-(2S,5R)5-alkylpyrrolidines as indolizidine and pyrrolizidine scaffolds

A new and short stereoselective route to the synthesis of enantiopure cis-2,5- disubstituted pyrrolidines as indolizidine or pyrrohzidine scaffolds has been developed. The method, which uses (S)-pyroglutamic acid as a chiral starting material, is based on the ring opening of N-protected gamma-lactams by alkyl phenyl sulfone carbanions, followed by desulfonylation and reductive amination of alkyl gamma-amino ketones. The diastereoselectivity depends on the substitution of the starting gamma-lactams, and on the alkyl group of the phenyl sulfone. Total cis diastereoselectivity was observed in the formation of tert-butyl 5-alkylprolinates. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).