Regioselective synthesis of cytotoxic 4-(1-alkynyl)-substituted 2-(5 H)-furanones

Abstract

4-(1-Alkynyl)-3-bromo- and 4-(1-alkynyl)-3-chloro-2(5 H)-furanones have been regioselectively synthesized in moderate to good yields by a new version of the Pd/Cu-catalyzed Sonogashira reaction involving treatment of 1-alkynes with 3,4-dibromo- and 3,4-dichloro-2(5 H)-furanone, respectively, in the presence of KF as a base. 4-(1-Alkynyl)-3-bromo-2(5 H)-furanones have been found to be able to undergo Stille-type and Suzuki-type reactions with aryl(tributyl)tins and arylboronic acids, respectively, to give 4-(1-alkynyl)-3-aryl-2(5 H)-furanones in modest to satisfactory yields. Some 4-(1-alkynyl)-substituted 2(5 H)-furanones so prepared have been found to exhibit significant cytotoxic activities, especially against human leukemia cell lines.