Palladium-catalyzed a-arylation of carbonyl compounds and nitriles

Palladium-Catalyzed a-Arylatlon of Carbonyl Compounds and Nitriles 

As far as the influence of the phosphine ligand in the catalyzed reactions is concerned, P(tBu)j is effective in most cases. The rate of the reductive elimination of enolate complexes containing this and other bulky phosphines is faster, and the scope of many couplings catalyzed by complexes with these ligands is broader. Recently, it has been found that a catalytic quantity of phenol causes a remarkable increase in the efficiency of ketone enolate arylation [382]. 

Formation of a CyjP-Pd-L (L = NHC) has been proposed as the catalyticaUy active species in the aryl amination and a-arylation of ketones by Nolan in a system starting from a paUadacyde containing an NHC [383]. 

Copper-catalyzed arylation of malonates [385] and other activated methylene compounds (malononitrile, ethyl cyanoacetate) [386] have also been reported. It is likely that the catalyticaUy active species is a Cu(I) enolate. 

Pd(II) complexes formed by oxidative addition of organic electrophiles to Pd(0) may react with amines, alcohols, or thiols in the presence of a base to give the corresponding key amido, aUcoxide, or sulfide complexes. These complexes undergo reductive ehmination to afford the new C-X (X = O, N, S) bond in the final organic product [104, 387] and the paUadium(O) species is regenerated. The palladium-catalyzed cyanation of aryl halides [388] is probably mechanistically related to these reactions. 

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A. Culkin, J. F. Hartwig, Palladium-Catalyzed a-Arylation of Carbonyl Compounds and Nitriles, Acc. Chem. Res. 2003, 36, 234-245. 

Palladium-catalyzed a-Arylation of Carbonyl Compounds and Nitriles. A variety of bases have been used in the palladium-catalyzed a-arylation of carbonyl derivatives. The pKa of the carbonyl moiety determines the choice of the base. For instance, a-arylation with ester derivatives requires the use of strong bases such as NaHMDS. The best yields for the arylation of t-butyl acetate were reported with LHMDS, whereas the arylation of f-butyl propionate occurred in higher yields in the presence of NaHMDS (eq 12). ... 

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