An expeditious synthesis of 1-(4-chlorophenyl)-3,3-dimethyl-2-butanone by a ligand-free palladium-catalyzed α-arylation of pinacolone:: Scale-up and effect of base concentration

An efficient and large-scale synthesis of I(4-chlorophenyl)-3,3-dimethyl-2-butanone (1) by an alpha-arylation of pinacolone (2) with 1-bromo-4-chlorobenzene (3) in the presence of palladium acetate and sodium t-butoxide in toluene is described. An increase in the concentration of sodium t-butoxide to 2.5 - 3.0 equivalents suppressed the formation of over-arylated products. These ligand-free conditions afforded a yield of 1 that was comparable to those obtained by using a ligand.