Asymmetric total synthesis of (+)-equilenin utilizing two types of cascade ring expansion reactions of small ring systems

Abstract

Enantioselective synthesis of (+)-equilenin 1 utilizing two types of cascade ring expansion reactions of small ring systems is described. The first key step is an asymmetric epoxidation–ring expansion reaction of cyclopropylidene derivatives to afford chiral cyclobutanones. We found that both the fructose-derived chiral ketone and the chiral (salen)Mn(III) complex were effective catalysts for the asymmetric induction. The second key step is the palladium-promoted cascade ring expansion–intramolecular insertion reaction of the isopropenylcyclobutanol. Solvents were an important factor for the diastereoselective formation of hydrindanes. By utilizing these methodologies, the asymmetric total synthesis of (+)-equilenin 1 has been accomplished.