Combining the power of Ti(III)-mediated processes for easy access to hydroxylated polycyclic terpenoids: synthesis of sesterstatin 1 and C-D rings of aspergilloxide.

A straightforward access to polyhydroxylated terpenoids based on two key titanocene(III)-mediated reactions is presented: the "head-to-tail" Barbier-type addition of prenyl chlorides to alpha,beta-unsaturated aldehydes, which allows the introduction of hydroxy groups at desirable positions of the acyclic precursor, and the subsequent bioinspired radical cyclisation. This methodology has been also used in the first total synthesis of pentacyclic sesterstatin 1 and a model compound of the C-D rings of aspergilloxide.