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 aldehyde 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 α-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 .