Assembly of the 1-azaspiro[5.5] undecane framework associated with perhydrohistrionicotoxin via electrocyclic ring-opening of a ring-fused gem-dichlorocyclopropane and trapping of the resulting π-allyl cation by a tethered, nitrogen-centered nucleophile

The carbamate-tethered gem-dichlorocyclopropane 27 was prepared, as a mixture of epimers, in ten steps from commercially available beta,gamma-unsaturated nitrile 9. Upon treatment with silver acetate under a range of reaction conditions, compound 27 underwent electrocyclic ring opening to give the corresponding pi-allyl cation that was then trapped by the reaction solvent, chloride ion, and/or acetate ion, and so affording varying mixtures of the chlorocyclohexenes 28, 29, 30, and/or 31. Sequential treatment of the same substrate with LiHMDS ( to generate the conjugate base of this carbamate) then silver tetrafluoroborate afforded the chlorocyclohexadiene 32 as the exclusive product of reaction. No spirocyclization product of the type 3 arising from trapping of the intermediate pi-allyl cation by the tethered carbamate was observed under any of the reaction conditions examined. In contrast, analogous treatment of the more rigid system 38 afforded compound 39 incorporating the 1-azaspiro[5.5] undecane framework associated with the potent neurotoxin perhydrohistrionicotoxin ( 2).