A Highly Practical and General Route for α-Arylations of Ketones Using Bis-phosphinoferrocene-Based Palladium Catalysts

Abstract

Well-defined, air-stable Pd complexes of bis-phosphinoferrocene family of catalysts have been studied in the arylation of various ketones with aryl chlorides and aryl bromides. Bis(di-tert-butyl)phosphinoferrocene (DtBPF)-based catalysts such as (DtBPF)PdCl2 and (DtBPF)PdBr2 have been identified as two of the most active catalysts for the α-arylation of a model reaction involving propiophenone and 4-chlorotoluene. The scope of the (DtBPF)PdCl2 catalyst has been efficiently expanded to the arylation of various ketones with aryl chlorides and bromides with up to 97% isolated yields, under relatively mild reaction conditions at low catalyst loadings. The efficacy of the (DtBPF)PdCl2 catalyst was demonstrated at very low catalyst loadings with S/C 10,000 for the difficult aryl bromide, 4-bromoanisole, and 2000 for the electron-neutral aryl chloride, 4-chlorotoluene, on ∼10-g scale with excellent isolated yields and lower Pd in the product (6 and 48 ppm, respectively). Comparative studies on the Pd:DtBPF molar ratios between in situ catalysts and preisolated catalysts revealed that preisolated (DtBPF)PdX2 (X = Cl, Br) are the catalysts of choice due to various practical reasons.