Sonogashira reaction reactivity

Palladium(0)-catalyzed coupling reactions - i. e. the Heck and Sonogashira reactions, the carbonylative coupling reactions, the Suzuki and Stille cross-coupling reactions, and allylic substitutions (Fig. 11.1) - have enabled the formation of many kinds of carbon-carbon attachments that were previously very difficult to make. These reactions are usually robust and occur in the presence of a wide variety of functional groups. The reactions are, furthermore, autocatalytic (i.e. the substrate regenerates the required oxidation state of the palladium) and a vast number of different ligands can be used to fine-tune the reactivity and selectivity of the reactions. 

In conclusion, the Pd chemistry of pyrimidines has its own characteristics when compared to carbocyclic arenes and other nitrogen-containing heterocycles such as pyridine and imidazole. One salient feature of halopyrimidines is that the C(4) and C(6) positions are more activated than C(2). As a result, 2-, 4- and 6-chloropyrimidines are viable substrates for Pd-catalyzed reactions and 4- and 6-chloropyrimidines react more readily than 2-chloropyrimidines. For the Sonogashira reaction, though, there is little difference in the reactivity among 2-, 4- and 5-positions of substituted halopyrimidines. Not only is the Sonogashira reaction a reliable method... 

Corma et al compared the use of different IL solvents and polyethylene glycol (PEG) using a carbopalladacycle complex as catalyst for Suzuki and Sonogashira reactions. They showed that the dialkyl-substituted imidazolium compounds had poor stability, reactivity and recyclability when compared with trialkyl substituted imidazolium compounds and PEG. They concluded that this result could be attributed to the stabilization of the Pd nanoparticles in the solvent. They showed that PEG was a better solvent since it gave better yields, had good stability, low cost and low toxicity. 

Activated and deactivated positions in halopyridines exhibit marked difference in reactivity in palladium chemistry, whereas little difference in reactivity was observed among 2-, 4-, and 5-positions of halopyrimidines for their Sonogashira reactions [84]. While 2-iodo-4,6-dimethylpyrimidine was the most suitable substrate for preparing internal alkyne 176, the reaction of either the corresponding bromide or chloride was less efficient [85]. Good to excellent yields were obtained for the preparation of alkynylpyrimidines from most terminal alkynes with the exception of propargyl alcohols. Later reports showed that... 

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,... 

Alkynyltins. These tins are the most reactive and couple with a variety of electrophiles smoothly, although there is no need to use these reagents if the Sonogashira reaction can substituteJ ... 

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