Sonogashira synthesis reactivity

Iodouracil derivatives are particularly reactive under normal Sonogashira conditions, as demonstrated by the room temperature synthesis of 5-ethynyluracil (eniluracil) 256 from trimethylsilylacetylene 254 and 5-iodouracil 255 <2006GJC580>. 

Scheme 10.7 depicts the synthesis of an OPE3 one-terminal wire compound by repeated Sonogashira cross-couplings [13c]. The synthesis takes advantage of the more reactive iodide as compared with the bromide, which allows for stepwise scaffolding. Thus, two concomitant Pd-catalyzed cross-couplings of 23 produced 24. The terminal alkyne obtained after desilylation was subsequently cross-coupled with 1 to afford 25. 

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,... 

Although solvents are known to have great effect on the reactivity, they are not often included in the mechanisms of metal catalysis. Far more often, metallic co-catalysts are employed that activate the substrate before transmetalation. In 2013, Koketsu reported the synthesis of cytotoxic furonaphthoquinones with the aid of CU2O and CuBr co-catalysts, which allowed Sonogashira coupling in combination... 

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