Palladium-Catalyzed Arylations of a-C-H Acidic Compounds

The alkylation of a-C—H acidic compounds is, historically, one of the most investigated reactions in organic chemistry. Thus, the results from a plethora of studies on this transformation are available, focusing on the enolate nucleophile or the alkyl electrophile, with asymmetric variants being described in detaU. In contrast. 

Hartwig Pd(dba)2, dppf or dtpf, KHMDS or NaOf-Bu, THF, reflux Buchwald Pd2(dba)3, BINAP orTol-BINAP, NaOf-Bu, THF, 70 °C Miura PdCl2-4LiCI, CS2CO3 (Arl instead of ArBr) 

The first attempts to use transition metal-catalyzed cross-coupling methodology to couple enolates with aryl halides were far from being broadly applicable, and involved less-attractive preformed zinc- or tin-enolates [210]. In addition, only ketones or acetates could be employed as enolate precursors. At that time, nickel was the predominant transition metal to mediate these couplings [211]. In an early contribution, CiufoHni arylated soft enolates in an intramolecular fashion with aryl halides using Pd(PPh3)4, along with NaH, in DMF at elevated temperatures [212]. This represented one of the first palladium-catalyzed arylations of enolates. 

For example, Hartwig used chelating ferrocene-based ligands, such as dppf or dtpf (l,l -bis(di-o-tolylphosphino)ferrocene), while Buchwald employed chelating 

Consequently, sterically hindered monophosphines, such as P(LBu)3, were tested and provided excellent yields in the a-arylation of C—H-acidic compounds [214], Today, monodentate phosphine ligands are broadly employed for this palladium-catalyzed arylation technology. 

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