Utilization of Sequential Palladium-Catalyzed Cross-Coupling Reactions in the Stereospecific Synthesis of Trisubstituted Olefins

✍ Scribed by Houpis, Ioannis N.; Shilds, Didier; Nettekoven, Ulrike; Schnyder, Anita; Bappert, Erhart; Weerts, Koen; Canters, Martine; Vermuelen, Wim

• Book ID: 126082052
• Publisher: American Chemical Society
• Year: 2009
• Tongue: English
• Weight: 578 KB
• Volume: 13
• Category: Article
• ISSN: 1083-6160
• DOI: 10.1021/op900015g

✦ Synopsis

A stereospecific synthesis of the drug-candidate 1 is described. The synthetic sequence, aimed at accomplishing modularity and cost savings, features a series of organometallic steps to afford stereospecifically the desired trisubstituded olefin active pharmaceutical ingredient. Key developments consist of a mild Sonogashira reaction of aryl bromide 7a with the polymerization prone propargyl alcohol and a stereospecific hydroalumination, Zn/Al exchange, and Pd-catalyzed cross-coupling sequence facilitated by the commercially available PEPPSI catalyst.