Lorraine M. Bateman

The abundance of the biaryl structural motif in natural products, in biologically active molecules and in materials chemistry has positioned aryl-aryl (Ar-Ar) bond formation high on the agenda of synthetic chemists. For decades well-known reactions such as the Mizoroki-Heck and Suzuki-Miyaura have been the methods of choice to furnish biaryls. More recently, however, alternative methods, most notably direct arylation via C-H activation, have become the focus of many research groups. Compared to traditional methods, direct arylation affords Ar-Ar compounds in fewer steps by removing the need for prefunctionalisation. Furthermore, given that either one or two hydrogens are targeted, less waste and good atom economy are features of this methodology. This critical review covers, in the main part, reports from January 1, 2006, to October 22, 2008 (117 references).

Aryl-heteroaryl coupling via double C-H activation is a powerful transformation that avoids the installation of activating groups. A double C-H activation of privileged biological scaffolds, 2-coumarins and 2-pyrones, is reported. Despite the rich chemistry of these molecular frameworks, the yields are very good. Excellent regioselectivity was achieved on the pyrones. This methodology was applied to the synthesis of flemichapparin C in three steps. Isotope effect experiments were carried out, and a mechanism is proposed.

A systematic investigation of the influence of substitution at positions C-2 and C-3 on the azulenone skeleton, based on NMR characterisation, is discussed with particular focus on the impact of the steric and electronic characteristics of substituents on the position of the norcaradiene-cycloheptatriene (NCD-CHT) equilibrium. Variable temperature (VT) NMR studies, undertaken to enable the resolution of signals for the equilibrating valence tautomers revealed, in addition, interesting shifts in the equilibrium.