Studies directed toward the synthesis of 4-deoxy-10-oxodihydrobotrydial, a naturally occurring botryane

Abstract

The Cp₂Ti(III)Cl-mediated opening of epoxides in α,β-unsaturated ester-appended substrates leads to a cascading 5-exo-trig radical cyclization followed by lactonization, yielding bicyclic lactone rings. Leveraging this strategic approach has become crucial in the construction of the core structures of many sesquiterpenoid natural products. In our present study, we have synthesized the [6,5,5] tricyclic framework of 4-deoxy-10-oxodihydrobotrydial in its 1,8-di-epi isomeric form in five simple steps, achieving an excellent overall yield using a titanocene(III) radical cyclization strategy as a key step, which fixes 3 consecutive stereocenters in the tricyclic core of the molecule.