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 sulfones afford enamine sulfones, which then undergo intramolecular alkylation to produce the corresponding cyclic enamines, This provides a convenient route to substituted piperidines, indolizidines, quinolizidines, and pyrrolizidines. The enantioselective total synthesis of the alkaloid (-)-indolizidine 167B (also named gephyrotoxin 167B) was thus achieved by the cycloaddition of (S)-2-(2-chloroethyl)pyrrolidine to 1-(p-toluenesulfonyl)-1-pentyne, followed by stereoselective reduction of the enamine moiety and reductive desulfonylation.