Synthesis of substituted piperidines, indolizidines, quinolizidines, and pyrrolizidines via a cycloaddition strategy using acetylenic sulfones as alkene dipole equivalents

The conjugate additions of beta- and gamma-chloroamines to acetylenic sulfo nes afford enamine sulfones, which then undergo intramolecular alkylation t o produce the corresponding cyclic enamines, This provides a convenient rou te to substituted piperidines, indolizidines, quinolizidines, and pyrrolizi dines. The enantioselective total synthesis of the alkaloid (-)-indolizidin e 167B (also named gephyrotoxin 167B) was thus achieved by the cycloadditio n of (S)-2-(2-chloroethyl)pyrrolidine to 1-(p-toluenesulfonyl)-1-pentyne, f ollowed by stereoselective reduction of the enamine moiety and reductive de sulfonylation.