STILLE Carbonylation

Pd-catalyzed Stille carbonylative cross-coupling Pd-catalyzed coupling of organostannanes and alkenyl-or aryl halides and CO to form ketones. 436... 

Novel chemistry involving 2-bromomethyl- and 3-bromomethylindoles was explored in two papers. An attanpted metal-mediated conpUng with a Grignard and a 2-bromomethylindole led unexpectedly to a dimaization reaction <05TL6983>. Bromomethylindoles were converted into the corresponding indolyl acetate daivatives utilizing a Stille carbonylation <05TL4577>. 

Chiral oxazolines Stille carbonylative coupling,4 Pd-catalyzed carbonylative coupling of Inflates of ketones and phenols with chiral amino alcohols provides )3-hydroxy amides, which cyclize to chiral oxazolines when treated with thionyl chloride. 

The Stille carbonylation continued to be explored in 2009 by Cai and colleagues, using their heterogeneous MCM-41-supported bidentate phosphine pal-ladium(O) complex. The authors reported the coupling of aryl iodides with organostannanes [71]. This method allows reusing the catalyst, and asymmetrical ketones were produced in high yields. 

When the above reaction is performed under an atmosphere of carbon monoxide, CO insertion occurs with the concomitant formation of two sigma carbon carbon bonds to give a ketone as product. This reaction is referred to as the Stille carbonylative coupling reaction (see equation 2 below). 

Diaryl ketones are important scaffolds in biologically active compoimds, and although several synthetic pathways are available in solution, their application in solid phase synthesis is rare. Yun et aL [85] have developed a high-throughput synthesis of diaryl ketones via a Stille carbonylation on solid phase. Immobilized arylstannanes 39 were subjected to Stille coupling with aryl halides in presence of carbon monoxide (Scheme 23). Not only did the reaction afford products of high yield and purity, but it was also tolerant towards most functional groups. 

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