Heck reactions of aryl chlorides

HECK REACTIONS OF ARYL CHLORIDES CATALYZED BY PALLADIUM/TRI-tert-BUTYLPHOSPHINE (E)-2-METHYL-3-PHENYLACRYLIC ACID BUTYL ESTER AND (E)-4-(2-PHENYLETHENYL)BENZONITRILE... 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

Scheme 6.2 Heck reactions of aryl chlorides involving air-stable phosphonium salts as ligand precursors.

Mukhopadhyay, S., Rothenberg, G., (oshi, A., Baidossi, M. and Sasson, Y. (2002) Heterogeneous palladium-catalyzed Heck reaction of aryl chlorides and styrene in water under mild conditions. Adv. Synth. Gated., 344, 348. 

Littke, A. F. Fu, G. C. A versatile catalyst for Heck reactions of aryl chlorides and aryl bromides under mild conditions./. Am. Chem. Soc. 2001, 123, 6989-7000. 

A series of palladium(O) mono-imidazolylidene complexes have also been prepared and used for the Heck reaction of aryl chlorides in [NBu4]Br.29 The authors report that two of their catalysts, (1,3-dimesi-tylimidazolylidene)(naphthoquinone)palladium(0) and (1,3-dimesitylimida-zolylidene)(benzoquinone)palladium(0) (Fig. 5) remain stable throughout the reaction and will couple even non-activated aryl chlorides in good yields. Clearly, the authors believe that the imidazolylidene complex is responsible for this activity. 

Scheme 10.3 Proposed catalytic cycle for the Heck reaction of aryl chlorides catalyzed by [ (C5H3)-2,6-(OP(/Pr)2)2Pd(CI) ] (3).

Selvakumar, K., Zapf, A. and BeUer, M. (2002) New palladium carbene catalysts for the Heck reaction of aryl chlorides in ionic liquids. Org. Lett., 4, 3031-3. 

Numerous ligands have been applied successfully to the Heck reaction, including phosphines, phosphites, palladacycles and carbenes. Of the reported ligands however, several stand out for their high activity and substrate scope. Perhaps the greatest advance of this chemistry was the discovery of ligands which enable the Heck reaction of aryl chlorides. Aryl... 

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