Aryl chlorides Sonogashira reaction

We synthesized uniform CU2O coated Cu nanoparticles from the thermal decomposition of copper acetylacetonate, followed by air oxidation. We successfully used these nanoparticles for the catalysts for Ullmann type amination coupling reactions of aryl chlorides. We synthesized core/shell-like Ni/Pd bimetallic nanoparticles from the consecutive thermal decomposition of metal-surfactant complexes. The nanoparticle catalyst was atom-economically applied for various Sonogashira coupling reactions. 

Although the Sonogashira reaction is normally performed with a copper cocatalyst, a copper-free, one-pot procedure for direct coupling with l-aryl-2-trimethylsilylacetylenes has been developed <2005T2697>. The procedure uses a mixture of palladium acetate and tri(o-tolyl)phosphine as catalyst in the presence of tetra- -butylammonium chloride... 

Unlike other cross-coupling reactions, for which the scope has rapidly expanded in recent years, the range of electrophilic substrates that can be used successfully in the Sonogashira protocol is still rather limited. Vinylic substrates (iodides, bromides, chlorides, triflates, and more recently tosylates) typically yield the best results. For aromatic substrates, iodides and triflates are preferred over bromides, which in turn give far better yields than aryl chlorides. This latter aspect of the reaction is particularly frustrating when one considers the recent advances in the activation of aryl chloride substrates for reactivity in other cross-coupling protocols. ... 

Aryl iodides, bromides, and inflates are used for Sonogashira coupling. But so far few smooth reactions of aryl chlorides with alkynes have been reported. On the other hand, smooth coupling takes place with alkenyl chlorides. The Pd-catalyzed reaction of 1-alkynes with alkenyl chlorides, which are inert in many other Pd-catalyzed reactions, proceeds smoothly without special activation of the chlorides. For example, cw-l,2-dichloroethylene (31) can be coupled with 1-alkynes smoothly, and the coupling has wide synthetic applications, particularly for the synthesis of enediyne structures [30]. The reaction of 31 with two different 1-alkynes is extensively used for construction of highly strained enediyne structures present in naturally occurring anticancer antibiotics such as espermicin and calichemicin [31,32]. The asymmetric (Z)-enediyne 34 can be prepared by a one-pot reaction of 31 with two different 1-alkynes 32 and 33. Similarly the asymmetric ( )-enediyne 37 was obtained in a one-pot reaction of 1-alkynes 33 and 23 with 1,2-dichloroethylene 35. 

Along with the aforementioned developments, several less common electrophiles, such as aryldiazonium salts [140], arenesulfonyl chlorides [141], triflates and tosylates [142], or tetraphenylphosphonium chloride [143], have successfully been appHed in the Sonogashira reaction in place of aryl halides. 

Tri-t-butyl phosphine can be more effective in the coupling of reluctant aryl bromides (Scheme 2.118). Bulky electron-rich biaryl phosphine ligands, such as 2385, can also promote the Sonogashira reaction of difficult aryl chlorides (Scheme 2.119). ° Interestingly, in this case, the presence of copper(I) salts inhibited the reaction, and the copper-free version provided better yields. Aryl tosylates, easily prepared from phenols, also couple under these conditions (Scheme 2.120). 

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