Wolff/Cope Approach to the AB Ring of the Sesterterpenoid Variecolin

A stereoselective
synthesis of the AB ring of the complex sesterterpenoid
variecolin is presented. Our strategy features the development of
a tandem Wolff/Cope rearrangement of α-diazo cyclobutyl ketones
for the construction of fused, 8-membered carbocycles. Preliminary
studies revealed a facile Wolff rearrangement but a difficult vinyl
ketene cyclobutane Cope rearrangement. We have leveraged an efficient
microwave-promoted tandem rearrangement to prepare the desired functionalized
cyclooctadienones that we envision as potential key intermediates
in the convergent synthesis of variecolin.