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Article

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

Supporting Info

Gabriela A. Grasa* and Thomas J. Colacot

Johnson Matthey Catalysis and Chiral Technolgies, 2001 Nolte Drive, West Deptford, New Jersey 08066, U.S.A.

Org. Process Res. Dev., 2008, 12 (3), pp 522–529

DOI: 10.1021/op7002503

Publication Date (Web): April 25, 2008

* Corresponding author. Telephone: 856-384-7039 . Fax: 856-384-7035. E-mail: grasag@jmusa.com.

This article is part of the

Transition Metal Mediated C-C and C-N Bond Formation

special issue.

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.