A Concise Synthesis of (-)-Indolizidines 209D and 209B

A general stereoselective synthetic route to 5-substituted and 5,8-disubstituted indolizidine alkaloids has been developed starting from commercially available L-proline. (-)-Indolizidines 209D and 209B were efficiently synthesized in 9.8% and 14.8% overall yields in seven and five-step reactions from readily available aldehyde 3 and ketone 10, respectively. The key steps of this synthesis involve a substrate-induced asymmetric addition of ethyl lithiopropiolate to aldehyde 3 or methyl ketone 10. and a two-step one-pot hydrogenation/cyclization sequence to construct the bicyclic skeleton.