L-776967

A new approach to 2,3-disubstituted cyclopentenones has been developed. This approach consists of a two-step protocol involving the cyclization of a Z-vinyl bromide under Barbier type conditions to form a cyclopentenol, which is then oxidatively rearranged to generate the cyclopentenone. The Z-vinyl bromide is in turn derived from a ruthenium catalyzed three-component coupling of an alkyne, an enone, and a HBr equivalent. A range of 2,3-disubstituted cyclopentenones has been generated, including short syntheses of jasmone and dihydrojasmone. Further applicability of this strategy is shown in the total syntheses of tetrahydrodicranenone B, rosaprostol, and a selective COX-2 inhibitor.

Exclusive Z-selectivity in the Ru-catalyzed bromoalkylation of alkynes with vinyl ketones is observed with aryl and other tertiary substituted acetylenic substrates, a feature that has led to an efficient synthesis of 2-(3,5-difluorophenyl)-3-[4-(methylsulfonyl)phenyl]-2-cyclopentenone, a COX-2 inhibitor.