A practical synthesis of the F-ring of halichondrin B via ozonolytic desymmetrization of a C(2)-symmetric dihydroxycyclohexene

C(2)-symmetric dihydroxycyclohexene 1 was desymmetrized via a one-pot Criegee ozonolysis/acylation protocol to afford acetal-lactone 2. Installation of the allyl side chain on the convex face of the bicyclic system and subsequent reduction provided the desired tetrahydrofuran 4 with the correct relative and absolute stereochemistries. Simple functional group manipulations led to the desired F-ring module 3 of halichondrin B.