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

Abstract

The carbamate-tethered gem-dichlorocyclopropane 27 was prepared, as a mixture of epimers, in ten steps from commercially available β,γ-unsaturated nitrile 9. Upon treatment with silver acetate under a range of reaction conditions, compound 27 underwent electrocyclic ring opening to give the corresponding π-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 π-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).