Asymmetric Synthesis of the Oxygenated Polycyclic System of (+)-Harringtonolide

A straightforward asymmetric synthesis of the cage oxygenated structure of (+)-harringtonolide has been accomplished for the first time. The key steps involved (i) a templated stereoselective IMDA reaction to build a highly functionalized cyclohexene ring D, (ii) functionalization of the cycloadduct, (iii) ring-closing metathesis providing the five-membered ring C, and finally (iv) a challenging one-step cascade cyclization of an epoxy-alcohol toward the target structure, whose mechanism was investigated.