Regioselective Functionalization of the Imidazole Ring via Transition Metal-Catalyzed C-N and C-C Bond Forming Reactions

Functionalized imidazole derivatives include compounds that are known to possess a broad range of significant biological properties or are important templates in medicinal chemistry. In the light of the importance of these heteroaromatic compounds 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 allowing for the construction of the heteroaromatic core of these substances by cyclization protocols. However, in recent years, much more attention has been focused on the design and development of efficient protocols that are based on the selective functionalization 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, including bioactive and/or naturally occurring compounds, which cannot be accessed by other means. This critical review with 439 references covers developments in this hot area of research up to July 2009 and includes a description of synthetically important, regioselective transition metal-catalyzed Csp(2)-N, Csp-N, Csp(3)-N, Csp(2)-Csp(2), and Csp-Csp(2) bond forming methods, their applications, and limitations.