APPLICATION OF A STEREOSPECIFIC INTRAMOLECULAR ALLENYLSILANE IMINO ENE REACTION TO ENANTIOSELECTIVE TOTAL SYNTHESIS OF THE 5,11-METHANOMORPHANTHRIDINE CLASS OF AMARYLLIDACEAE ALKALOIDS

Enantioselective total syntheses of the pentacyclic 5,11-methanomorpha nthridine Amaryllidaceae alkaloids (-)-montanine (1), (-)-coccinine (2 ), and (-)-pancracine (3) were accomplished using an intramolecular co ncerted pericyclic allenylsilane imino ene cycloaddition as a key step . These complex natural products were constructed starting from readil y available enantiomerically pure epoxy alcohol 15 which was converted to allenylsilane aldehyde 28 via an efficient nine-step sequence. The imine generated from aIdehyde 28 and iminophosphorane 47 underwent a stereospecific thermal imino ene reaction to afford key intermediate c is aminoalkyne 49. It was possible to transform this compound via Lind lar hydrogenation followed by an intramolecular Heck reaction to seven -membered ring tetracycle 51. This olefinic intermediate could be func tionalized through its epoxide to yield alpha-hydroxymethyl intermedia te 54, and then pentacyclic alcohol 64. Procedures were then developed to convert this material to the enantiomerically pure alkaloids 1-3. A formal enantioselective total synthesis of (-)-brunsvigine (4) was a lso achieved via triol 72.