Total Synthesis of (−)-Coriolin

An efficient synthetic method for (−)-coriolin has been developed on the basis of a [3+2] cycloaddition reaction of a 1-(methylthio)-2-siloxyallyl cationic species and vinylsulfides. An enantiomerically pure C-ring unit was prepared through optical resolution of five-membered allyl ester 6b using a lipase. The first [3+2] cycloaddition reaction of C-ring unit ( S )-7 gave bicyclic ketones 8 and 9, which were easily converted into vinyl sulfide 11. Stereoselective construction of the A-ring was achieved by the second [3+2] cycloaddition reaction of the BC-ring unit. New methods for introduction of the oxygen functional groups to the triquinane skeleton were also developed for the last stages of the total synthesis. Thus, the C7 hydroxyl group was introduced by epoxidation of dienol silyl ether 17, and stereocontrolled construction of the spiro epoxide moiety was accomplished on the basis of a Darzens-type reaction.