Total synthesis of (-)-bitungolide F and determination of its absolute stereochemistry

[GRAPHICS] A highly convergent total synthesis of bitungolide F leading to the assignment of its absolute stereochemistry is described. The key steps include a Horner-Wadsworth-Emmons olefination to construct the C7-C8 bond, a Wittig reaction to introduce the conjugate E,E-olefinic moiety in the molecule, and finally a ring-closing metathesis reaction to construct the six-membered alpha,beta-unsaturated delta-lactone of the molecule. Modified Evans's syn-aldol reaction, using Crimmins's protocol, was used to install the stereochemistries at the C4 and C5 centers. The stereochemistry at C9 was introduced by means of hydroxy-directed reduction of the C9 keto using Evans's protocol.