Construction of the Tricyclo

Histrionicotoxin derivatives have long been attractive targets for synthetic chemists as a result of their useful neurophysical properties, low natural abundance, and the unique structural features of the azaspiro5.5]undecane ring system. Utilizing our tandem pinacol rearrangement-ene strategy and regiospecific Baeyer-Villiger oxidation as key steps, we have successfully synthesized an advanced synthetic intermediate, spiro5.4]decane 4, which has previously been converted to (+/-)-perhydrohistrionicotoxin (5b). Pinacol rearrangement of simple Diels-Alder derived bicyclo2.2.2]octene system 2a, followed by an ene reaction, led to the efficient formation of the highly fuctionalized tricyclo5.3.1.0(1,5)]undecane system 1a. This tricyclic system 1a was selectively transformed into spiro5. 4]decane system 4 via a regiospecific Baeyer-Villiger oxidation reaction. We also report the results of systematic studies of Baeyer-Villiger oxidation reactions of tricyclo5.3.1.0(1, 5)]undecanone systems to elucidate the origin of the regioselectivity of this process.