Sonogashira reactions, with

Pyrazinone bearing a phenylalkynyl substituent at position C-3, was prepared in 47% yield via Sonogashira reaction with 7 equiv of phenylacetylene in a mixture of toluene/triethylamine (2 1) using Pd[P(Ph3)2]Cl2 and Cul as the catalyst system (Scheme 37). 

Advantage has been taken of the aforementioned observations in the synthesis of a terthiophene natural product, arctic acid (147) [123]. Pd-catalyzed carbonylation of bromobisthiophene 25, obtained from the Kumada coupling of 2-thienylmagnesium bromide and 2,5-dibromothiophene, gave bithiophene ester 144, which was converted to iodide 145 by reaction with iodine and yellow mercuric oxide. Subsequent propynylation of 145 was then realized using the Sonogashira reaction with prop-l-yne to give bisthienyl alkyne 146, which was subsequently hydrolyzed to 5 -(l-propynyl)-2,2 -bithienyl-5-carboxylic acid (147), a natural product isolated from the root of Arctium lappa. 

Van der Eycken s group developed a silver(I)-mediated synthesis of substituted furo[2,3-6]pyrazines.53 Starting from -methoxybenzyl-protected 3,5-dichloropyr-azine-2(l//)-ones 26 (Scheme 5.13), after a regioselective microwave-assisted Sonogashira reaction with various terminal alkynes, the cycloisomerization reaction could occur using AgOTf (2 mol%) with trifluoroacetic acid (TFA, 5 equiv) to yield... 

Synthesis of phorboxazole A has been accomplished [8, 9], The C(46) terminus of phorboxazole A was modified to incorporate a biotin-terminated linker via a direct Sonogashira reaction with tris-polyethyleneglycol vinyl iodide-biotin ester using catalytic PdCljlPPh, ), Cul, and NEt, in THE This process demonstrated the utility of mild C-C bond formation in the context of the phorboxazole architecture and provided a potential affinity probe [10],... 

Scheme 15.49. Palladium-catalyzed Sonogashira reaction with trimethylsilylacetylene.

Choudhary BM, Madhi S, Chowdari NS, Kantam ML, Sreedhar B (2002) Copper-free Sonogashira reaction with transition-metal nanoparticles. J Am Chem Soc 124 14127... 

The first report of a Sonogashira coupling reaction of an oxazole was by Yamanaka in 1987. Oxazoles substituted with bromine at the 4- or 5-positions were coupled with phenylacetylene yielded the alkyne in 83% and 89% yield, respectively. The Sonogashira reaction with 2-halooxazoles was not attempted however, 2-halothiazoles and 2-halo-A -methylimidazoles were subjected to Sonogashira conditions. Yields in both cases were low and not synthetically useful. 

A variation of this transformation to functionalize thiazoles has been reported by Panek and co-workers and extended to triflates as the electrophilic coupling partners. Here 2-, 4-, and 5-trifloyl thiazoles were demonstrated to undergo the Sonogashira reaction with terminal alkynes as... 

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... 

In the first of three widely used indole syntheses involving Pd-catalyzed alkyne conpling with o-haloanilines, this chapter covers the Yamanaka-Sakamoto-Sonogashira reaction. This two-step process features an initial Sonogashira reaction with a terminal alkyne [1] followed by a facile indohzation, which was first uncovered by Yamanaka, Sakamoto, and coworkers (Scheme 1, equations 1 ) [2-9], The intermediate C-3 palladium species can undergo carbonylation with CO to give indole-3-carboxylates (equation 4) [7,9]. For reviews, see Sakamoto, Kondo, and Yamanaka [10] and Heravi and Sadjadi [11]. 

The low volatility of ionic liquids and the easy separation of catalysts (which usually remain in these polar media) have made ionic liquids an interesting alternative to typically used organic solvents. Rather unsatisfactory results have been obtained in both copper-mediated [36] and copper-free [37] Sonogashira reactions, with aryl iodides being the only aromatic electrophiles coupled at reaction temperatures between 60 and 80 °C. It should further be noted that imidazolium-based ionic liquids are not necessarily innocent solvents, but can be deprotonated in the presence of bases to generate N-heterocycUc carbenes (NHCs). 

Reddy and collaborators reported a new one-pot, three-component procedure toward the synthesis of novel 4-phenyl-2-[3-(alkynyl/alkenyl/aryl) phenyl] pyrimidine libraries starting with the Michael addition of enaminone 64 with 3-bromobenzimidamide hydrochloride (65) (Scheme 28) (13S75). This was followed by a cyclization, an isomerization, a dehydration, and a subsequent Sonogashira reaction with terminal alkynes or a Suzuki reaction with arylboronic acids or a Heck coupling reaction with alkenes. 

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