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-methanomorphanthridine Amaryllidaceae alkaloids (-)-montanine (1), (-)-coccinine (2), and (-)-pancracine (3) were accomplished using an intramolecular concerted pericyclic allenylsilane imino ene cycloaddition as a key step. These complex natural products were constructed starting from readily 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 cis aminoalkyne 49. It was possible to transform this compound via Lindlar hydrogenation followed by an intramolecular Heck reaction to seven-membered ring tetracycle 51. This olefinic intermediate could be functionalized through its epoxide to yield alpha-hydroxymethyl intermediate 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 also achieved via triol 72.