Application of intramolecular pericyclic imino ene reactions of allenylsilanes to enantioselective total syntheses of the 5,11-methanomorphanthridine Amaryllidaceae alkaloids (-)-coccinine, (-)-montanine and (-)-pancracine

A new type of thermal intramolecular pericyclic ene reaction of allenylsilane imines and allenylsilane aldehydes was developed. Allenylsilane imine 105 was cyclized under mild thermal conditions to stereospecifically produce cis amino alkyne 106 in good yield. Similarily, thermal cyclization of allenylsilane imine 123, followed by desilylation, afforded a six-membered cyclic amino acetylene 127 in 65% as a single cyclization product. The silyl group on the allene was proven to be necessary for the imino ene reaction to proceed. It was also found that thermal cyclization of allenylsilane aldehydes 104 and 122 stereospecifically generated hydroxy alkynes 129 and 131, respectively.; Enantioselective total syntheses of the pentacyclic 5,11-methanomorphanthridine Amaryllidaceae alkaloids ({dollar}-{dollar})-montanine (1), ({dollar}-{dollar})-coccinine (2) and ({dollar}-{dollar})-pancracine (3) were accomplished using this intramolecular pericyclic allenylsilane imino ene chemistry as a key step. These complex natural products were synthesized starting from readily available enantiomerically pure epoxy alcohol 141. This epoxide was converted to allenylsilane aldehyde 164 via an efficient sequence of reactions. The imine 192/193 generated from aldehyde 164 underwent a stereospecific thermal imino ene reaction to afford key intermediate amino alkyne 195. It was possible to transform this compound via an intramolecular Heck reaction to tetracycle 201, which could be cleanly functionalized to yield {dollar}alpha{dollar}-hydroxymethylene intermediate 203, and then pentacyclic alcohol 219. Procedure were then developed to convert this material to the enantiomerically pure alkaloids 1-3. A formal enantioselective total synthesis of ({dollar}-{dollar})-brunsvigine (4) was also achieved.