A Cycloaddition Approach to Breynolide.

Abstract A novel approach to the functionalized hydrobenzothiophene subunit of the sesquiterpene breynolide (3) has been developed. The sequence features the Diels-Alder reaction of the vinyl sulfones 12 and 13 with the Danishefsky diene 9 to give the cycloadducts 14 and 16 as the major products. Reduction of the sulfone moieties of 14 and 16 gave the sulfides 20 and 21, respectively. Subsequent dipolar cycloaddition of 20 and 21 with a functionalized nitrile oxide gave the corresponding adducts 24 and 25, which possess functionality suitable for elaboration into breynolide (3).