Regioselective C-C bond formation reactions on 2,3-dibromo- and 2,3,5-tribromobenzofuran as an access to multiply substituted benzofurans. Total syntheses of eupomatenoids 3, 4, 5, 6, and 15

Regioselective C-C-bond formation reactions at 2,3-dibromobenzofuran (1) and 2,3,5-tribromobenzofuran (6) were studied. Pd-catalyzed Sonogashira and Negishi cross-coupling occurred with perfect regioselectivity at carbon atom C-2 to provide 2-substituted 3-bromobenzofurans (12, 14) and 3,5-dibromobenzofurans (17, 18) in 50-91% yield. A regioselective displacement of the bromine substituents in 3,5-dibromobenzofurans 18 was achieved by a halogen-metal exchange reaction at carbon atom C-3 and by a Nicatalyzed Kumada cross-coupling at C-5. The methodology was applied to the synthesis of eupomatenoids 3, 4, 5, 6, and 15 (5). The synthesis of these compounds was achieved in overall yields of up to 60%.