A novel route to the F-ring of halichondrin B. Diastereoselection in Pd(0)-mediated meso and C(2) biol desymmetrization.

Both sigma and C(2) symmetric diol diacetates were synthesized via two-directional chain elongation. A palladium-mediated, ligand-controlled C(2) diol desymmetrization provided the desired tetrahydrofuran with the correct relative and absolute stereochemistries. Simple functional group manipulation led to the desired F-ring of halichondrin B. Desymmetrization of the meso substrate enantioselectively provided the diastereomer, leading to a refinement of our understanding of the transition state model. [reaction: see text]