Alpha-Arylation of Acetophenones via a Radical Mechanism

Abstract

Alpha-arylation is an important reaction which is commonly used in the synthesis of many pharmaceuticals. To catalyze these reactions palladium catalysts are usually used, however copper and nickel also can be used. Alpha-arylation is also possible without any transition metal via the SRN1 reaction. Recently, Klein Gebbink et al. found an alpha-arylated side product, namely 1-(4-Phenylphenyl)-2-(4-acetylphenyl)ethanone, in the direct arylation reaction between 4bromoacetophenone and benzene. Using their conditions as a starting point, different conditions were tried in order to optimize the reaction between acetophenone and bromobenzene. Yields of up to 49% of 2phenylacetophenone were obtained when using bromobenzene and 57% of 2-(1-naphthyl)-1phenylethanone when using 1-bromonapthtalene. Alpha-arylation of an ester was attempted, which did not yield any arylated product. This was most likely due to KOtBu not being strong enough to deprotonate tert-butyl acetate. Furthermore, in an alpha-arylation reaction in the presence of carbon monoxide, a diketone was obtained in 6% yield. This shows that the used system is able to perform free-radical carbonylation.