Regioselective Threefold Aromatic Substitution of Benzoic Acid Derivatives by Dearomatization, Regioselective Functionalization, and Rearomatization

摘要

Substituted arenes are ubiquitous and important in various fields of modern science. They occur in natural products, in drugs, in agrochemicals, as ligands in catalysis, in biology, and in materials science. Despite the high efficiency of the classical functionalization methods, such as electrophilic, nucleophilic, and homolytic aromatic substitution, development of novel processes for regioselective functionalization of arenes is still of importance.Transition-metal-mediated couplings have become highly valuable and recent research in this area has focused on the direct C—H functionalization of arenes and heteroarenes. In many of these transformations a heteroatom or a functional group is necessary to direct the reaction towards a regioselective ortho functionalization. More recently, reports have appeared on arene functionalization in meta position of a directing group' and even a few reports on the para arylation have been disclosed. An alternative elegant approach for arene functionalization was introduced by Linker and co-workers (Scheme l). Benzoic acid derivatives were regioselectively ipso-alkylated by alky-lative Birch reduction and subsequent decarbonylative rearomatization to eventually afford the corresponding ipso-substituted arene.