Regioselective functionalization of the imidazole ring via transition metal-catalyzed C–N and C–C bond forming reactions

Functionalized imidazole derivatives in- clude compounds that are known to possess a broad range of significant biological properties or are im- portant templates in medicinal chemistry. In the light of the importance of these heteroaromatic com- pounds a great deal of attention has been given to their synthesis and, in the past years, a number of methods has been described in the literature allow- ing for the construction of the heteroaromatic core of these substances by cyclization protocols. Howev- er, in recent years, much more attention has been fo- cused on the design and development of efficient protocols that are based on the selective functionali- zation of the imidazole ring at the N-1, C-2, C-4 or C-5 position via transition metal-catalyzed reactions and enable the synthesis of imidazole derivatives, in- cluding bioactive and/or naturally occurring com- pounds, which cannot be accessed by other means. This critical review with 439 references covers devel- opments in this hot area of research up to July 2009 and includes a description of synthetically important, regioselective transition metal-catalyzed Csp2-N, Csp-N, Csp3-N, Csp2-Csp2, and Csp-Csp2 bond form- ing methods, their applications, and limitations.