Synthesis of Substituted Piperidines, Indolizidines, Quinolizidines, and Pyrrolizidines via a Cycloaddition Strategy Using Acetylenic Sulfones as Alkene Dipole Equivalents

The conjugate additions of β- and γ-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.