Sonogashira cross coupling Synthesis applications

The terminal alkyne can also be generated in situ via copper-free Sonogashira cross-coupling of trimethylsilyl acetylene (5a) and aryl halides 6 and subsequent cleavage with TBAF, caibonylation, and cyclization (Scheme 26) (20090L(11)3210). This microwave-assisted sequence allows the rapid synthesis of the title compounds in moderate to good yields. Each compound can be easily varied with exception to trimethylsilyl acetylene. The application of electron-rich aryl bromides and iodides expectedly decreases the yields. 

More recent applications of the Sonogashira reaction in PUFA synthesis include Spurs and Rodriguez s synthesis of maresin 1 (56) [72], a potent anti-inflammatory lipid mediator derived from DHA (7). As shown in Scheme 3.21, the Sonogashira cross coupling reaction of alkyne 82, bearing an unprotected secondary alcohol, with vinyl iodide 83, provided compound 84. Then, removal of the TES group, Boland reduction of the triple bond, and subsequent hydrolysis of the methyl ester afforded maresin 1 (56). 

Dakin, L.A., Langille, N.F., and Panek, J.S. (2002) Synthesis of the Cl -Cll oxazole-containing side chain of leucascandrolide A. Application of a Sonogashira cross-coupling. J. Org. Chem., 67, 6812-6815. 

The Castro-Stephens reaction is the cross coupling of a copper acetylide (1) and an aryl or vinyl halide (2) to give a disubstituted alkyne (3). The reaction, which shares some common elements with the Sonogashira, Cadiot-Chodkiewicz, Rosenmund-von Braun, Hay, and Glaser coupling reactions, was discovered by Stephens and Castro in the early 1960s and has found some applications in synthesis. " ... 

There are numerous applications of the Sonogashira reaction in the solid phase synthesis of molecules of biological interest, in some cases as part of a synthetic sequence but in the majority of examples for scaffold diversification purposes, and only a few can be mentioned here. Takahashi and coworkers prepared a Ubrary of 96 cross-conjugated dienones by subjecting a pendant acetylenic moiety on a cyclopentenone scaffold, attached to polystyrene via the Ellman THP-linker, to a Sonogashira coupling reaction... 

---