Aryl chlorides Sonogashira coupling

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. 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

Scheme 5. Palladium-catalyzed Sonogashira coupling of aryl chlorides according to Plenio and Kollhofer.

General Procedure for Sonogashira Coupling of Alkynes and Aryl Chlorides According to Plenio and Kollhofer[47]... 

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. ... 

Palladium catalyst supported on poly(4-methylstyrene) can be used for biphasic nonpolar Suzuki and Sonogashira coupling of aryl bromides and chlorides with good product yields. The catalyst can be recycled five times with negligible decrease in the activity. 

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. 

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