Rhodium(III) and hexabromobenzene - A catalyst system for the cross-dehydrogenative coupling of simple arenes and heterocycles with arenes bearing directing groups

Abstract

The biaryl scaffold is of great importance in many fields, such as biologically active molecules and materials. Lately, its synthesis has been greatly facilitated by the advent of crosscoupling reactions. Nevertheless, the development of more step-and atom-economic transformations is highly desirable. The development of direct arylation reactions (coupling of a preactivated partner with a benzene derivative) was a first approach to this goal.[1] However, more recently, catalyst systems that enable the oxidative cross-dehydrogenative coupling (CDC) of two non-prefunctionalized arenes have emerged as an attractive alternative.[2] Initial studies in this challenging field showed that palladium catalysts are particularly suited for this transformation.[3, 4] Furthermore, very recently, [RhIIICp*]-catalyzed (Cp*=C5Me5) formations of biaryls through twofold C-H activation were developed.[5-8] The key to success was the application of aryl halides as the C-Hcoupling partner.[9] Indeed, these halogenated substrates are believed to not only act as the coupling partner, but also as the cooxidant and/or catalyst modifier (Scheme 1).[10] This intriguing and multiple role of the haloarenes was, however, a limitation of the catalyst system, since only halogen-substituted benzene derivatives could be used successfully. Herein, we report an unprecedented application of hexabromobenzene (C6Br6) as the key additive that enables a highly chemo- and regioselective dehydrogenative cross-coupling of benzamides with a variety of simple benzene derivatives. Furthermore, this unique and crucial reactant opens the door for the application of this modern strategy to the direct functionalization of synthetically useful heterocycles. Besides tremendously expanding the scope of this CDC, the use of this halogenated species allows the amount of the coupling partner to be decreased (in some cases down to 3 equiv). © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.