ENANTIOSELECTIVE SYNTHESIS OF PUMILIOTOXIN-251D - A STRATEGY EMPLOYING AN ALLENE-BASED ELECTROPHILE-MEDIATED CYCLIZATION

The enantioselective synthesis of pumiliotoxin 251D (1) (nine steps, 6.3% overall yield) is described in which the Pd(II)-mediated cyclization of the optically pure allenic amine 6 to give pyrrolidine 7a plays a central role. The functionality that the allene moiety imparts to 7a allows for rapid transformation to the enantiomerically pure bicyclic lactam 9. A stereocontrolled aldol elimination sequence was carried out on 9 to establish the geometry of the exocyclic alkene of 1.