Applications of the Sonogashira Reaction

Alkyne cross-coupling is also an important tool in the assembly of unique nanoarchitectures to investigate fundamental stmcture-property relationships. One pertinent example by Haley et al. [169] is the synthesis of DBA trefoils 61 and 62, which were prepared by a sequential Sonogashira cross-coupling/Pd-mediated 

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Probably the first industrial application of the Sonogashira reaction was in the production of Terbinafin 148, an anti-fungal agent developed by Sandoz (now Novartis) [99]. This was the cornerstone of a second generation process that consisted of less steps and was both more environmentally friendly and more economic than the first generation process. The new process was invented by chemists from Banyu Pharmaceutical and licensed by Sandoz [100]. Further... 

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). 

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... 

Elegant synthetic applications of carbonylative Sonogashira reactions were described by Muller and his group. For example, in 2005 they succeeded in producing palladium-catalyzed one-pot, four-component carbonylations for the... 

Helicenes 112-114 were all synthesized from 111 through application of the Sonogashira cross-coupling reaction, demonstrating the versatility of this building block (Fig. 6.8). H NMR spectroscopy of double hehcal compounds 112 and 113... 

The Sonogashira reaction is a transition metal-catalyzed coupling reaction which is widely used for the preparation of alkyl-, aryl- and diaryl-substituted acetylenes (Table 4.7) [120]. This reaction is a key step in natural product synthesis and is also applied in optical and electronic applications. Sonogashira reactions involve the use of an organic solvent with a stoichiometric portion of a base for capturing the... 

The Sonogashira reaction frequently serves as a platform for the construction of indoles, and we will explore this application in Chapter 3, but it also is a valuable method for the preparation of alkynyl pyrroles. 

Application of the Corey-Fuchs olefination to thioxanthone affords the 1,1-dibromoalkene 366 from which the 1,1-bis(trimethylsilylethynyl)alkene can be obtained by a double Sonogashira coupling reaction. Desilylation yields the 1,1-diethynylalkene (Scheme 86) <2004JA3108>. 

The applications of microwave chemistry to organic chemistry are too numerous to mention. A few representative examples will be given to illustrate the scope and utility. Microwave chemistry is widely used in synthesis. Examples include the Heck reaction (reaction 13-10)," the Suzuki reaction (reaction 13-12)," the Sonogashira reaction (reaction 13-13)," Ullman type couplings (reaction... 

More recently, Lautens has also employed l-(2-iodophenyl)-pyrrole as a bifunctional aryl iodide/acceptor for the synthesis of substituted pyrrolo[l,2]quinolines (Scheme 34)[82], During Catellani s application of the Cassar-Sonogashira reaction to the ort/m-alkylation sequence [70] it was found that alkynes can undergo further carbopalladation reactions with arylpalladium(II) species. It was this reactivity which led Lautens to explore the use of bromoalkylalkynes as species which can undergo an ort/zo-alkylation, followed by a cyclocarbopalladation onto the alkyne,... 

Copper Reactants. Application of the Pd/Cu-catalyzed cross-coupling, the Sonogashira reaction, with monosubstituted or protected acetylene gives rise to a variety of ethynyl-heteroarenes (Schenae 27). Reactions with trimethylsilylacetylene or phenylacetylene in... 

It is very unlikely that future research in this area will provide the answers to all of the problems associated with the Sonogashira reaction. Whilst for large-scale industrial applications the main considerations are price, simplicity and robustness of the catalytic system, the small-scale syntheses that are associated with pharmaceuticals will seek catalytic systems tailored to minimize adverse side reactions and the loss of precious substrates. Clearly, there is still much to be done, and many surprises lie in wait ... 

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