Sonogashira coupling reaction palladium chemistry

In this experiment, we will conduct some modern organic chemistry using a palladium catalyst. It is a rare opportunity for students in undergraduate laboratories to experience this powerful chemistry. We will react the lodosubstituted aromatic compounds, shown below, with 1-pentyne, 1-hexyne, or 1-heptyne in the presence of the catalysts, palladium acetate and cuprous iodide, to yield 4-substituted-l-pentynyl, 4-substituted-l-hexynyl, or 4-substituted-l-heptynylaromatic compounds. This reaction is called the Sonogashira coupling reaction. The reaction will be carried out in refluxing 95% ethanol as the solvent. In addition, piperazine will be employed both as a base and as a hydride donor. 

Bohm, V. P. W., Herrmann, W. A. Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions, 13 a copper-free procedure for the palladium-catalyzed Sonogashira reaction of aryl bromides with terminal alkynes at room temperature. Eur. J. Org. Chem. 2000,3679-3681. 

The field of palladium catalysis is also progressing rapidly. The Tsuji-Trost and Mizoroki-Heck reactions have been mentioned earher, however other C-C coupling reactions (Miyaura-Suzuki, Sonogashira and Stille) are now extensively used in organic chemistry, and the search for non-polluting Sonogashira and Miyaura-Suzuki reactions is being actively pursued. 

In conclusion, the fantastically diverse chemistry of indole has been significantly enriched by palladium-catalyzed reactions. The accessibility of all of the possible halogenated indoles and several indolyl triflates has resulted in a wealth of synthetic applications as witnessed by the length of this chapter. In addition to the standard Pd-catalyzed reactions such as Negishi, Suzuki, Heck, Stille and Sonogashira, which have had great success in indole chemistry, oxidative coupling and cyclization are powerful routes to a variety of carbazoles, carbolines, indolocarbazoles, and other fused indoles. 

Some of the optimized procedures for Stille and Sonogashira reactions involve the addition of copper cocatalysts to accelerate the cross-coupling procedures. A word of caution should be provided on the role of these additives in Pd-catalyzed amination procedures. Beletskaya and Davydov have reported the arylation of benzotriazole and of diary-lamines in polar organic or aqueous organic solvents using a combination of palladium and copper as catalyst.The arylation of amino acids has been reported under similar conditions.However, these reaction conditions are similar to classic Ullmann procedures for the synthesis of arylamines, except for the addition of palladium to the reaction mixture. In one case, subsequent work showed that the palladium species was not an essential component and that copper alone was the true catalyst in their reactions. An unusual accelerating effect of amino acid coordination to copper was used to explain the low-temperature Ullmann conditions. Beletskaya, however, showed that lower yields and a mixture of N1 and N2 arylation products were observed from the reactions of benzotriazole in the absence of copper and no reaction was observed in the absence of palladium. The conditions for this chemistry are, however, distinct enough from those of the majority of the aryl halide aminations to support the idea that a different mechanism may operate. 

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