A novel palladium-mediated coupling approach to 2,3-disubstituted benzo(b)thiophenes and its application to the synthesis of tubulin binding agents.
[structure: see text]. Flexible, 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-ethynylphenyl 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.
Flynn
B L
BL
Department of Chemistry, The Faculties, Australian National University, Canberra, ACT, 0200, Australia. flynn@rsc.anu.edu.au
Verdier-Pinard
P
P
Hamel
E
E
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D003078:Colchicine / Q000737:chemistry; D006801:Humans; D010165:Palladium / Q000737:chemistry*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D013876:Thiophenes; D014404:Tubulin; C088015:benzothiophene; D010165:Palladium; D003078:Colchicine