Asymmetric Synthesis of All Eight Seven-Carbon Dipropionate Stereotetrads

Enantiopure cycloheptadienyl sulfones 6 and 7 are diastereoselectively epoxidized to yield
epoxyvinyl sulfones 8, 9, 14, and 16 in high yields and diastereomeric ratios. Syn and anti methylation of
epoxides 8, 9, 14, and 16 enables access to all eight possible diastereomeric stereotetrads, seven of which
are commonly found in polypropionate natural products. Anti methylations of the above epoxides are possible
by either the reaction of methyl organometallics promoted by copper(I), or via reaction with trimethylaluminum
to yield stereotetrads 11, 12, 22, and 24. Syn methylations are achieved via Lawton SN2‘ reaction in the
case of stereotetrads 10, 15, and 38, while stereotetrad 13 is accessed by an oxidation/reduction alcohol
inversion sequence from stereotetrad 11. All stereotetrads were obtained in high diastereomeric ratios and
yields, and their relative stereochemistry was confirmed by X-ray crystallography. Oxidative cleavage of
the cyclic stereotetrads yields termini-differentiated acyclic heptanyl stereotetrads ready for use in building
larger fragments in the course of target syntheses.