A Novel Palladium-Mediated Coupling Approach to 2,3-Disubstituted Benzo[ b ]thiophenes and Its Application to the Synthesis of Tubulin Binding Agents

Flynn, BernardVerdier-Pinard, PascalHamel, Ernest2015-12-101523-7060http://hdl.handle.net/1885/67303Flexible, convergent access to 2,3-disubstituted benzo[b]thiophenes has been developed. The most concise approach involves sequential coupling of o-bromoiodobenzenes with benzylmercaptan and zinc acetylides to give benzyl o-ethynylpnenyl sulfides which react with iodine to give 3-iodobenzo[b]thiophenes in a 5-endo-dig iodocyclization. These iodides can be further elaborated using palladium-mediated coupling and/or metalation techniques. This method has been applied to the synthesis of some novel tubulin binding agents.Keywords: antineoplastic agent; benzothiophene; colchicine; palladium; thiophene derivative; tubulin; article; catalysis; cell culture; chemistry; human; protein binding; structure activity relation; synthesis; Antineoplastic Agents; Catalysis; Colchicine; Humans;A Novel Palladium-Mediated Coupling Approach to 2,3-Disubstituted Benzo[ b ]thiophenes and Its Application to the Synthesis of Tubulin Binding Agents200110.1021/ol00671792015-12-10