Development and Application of Effective Protocols for the Synthesis of Arylheteroarenes and Biheteroaryls, Including Bioactive Derivatives, by Highly Regioselective Transition Metal-Catalyzed Direct Intermolecular Arylation Reactions of Five-Membered Heteroarenes with (Hetero)aryl Halides

摘要

The past decade has witnessed significant progress in highly regioselective direct arylation of azoles with aryl halides. This account aims to summarize recent progress in the development and application of these reactions. In particular, it describes and comments on the results obtained in the development of efficient protocols for the selective Pdcatalyzed direct C-5 arylation of 1-aryl-1H-imidazoles, 1-benzyl-1H-imidazole and 1-methyl-1H-imidazole and the highly regioselective Pd-catalyzed and Cu-mediated direct C-2 arylation of azoles, including free (NH)-imidazole, - benzimidazole and -indole. The utility of these novel protocols for the concise and efficient preparation of 1,5-diaryl- and 1,2-diaryl-1H-imidazoles, including derivatives of potential pharmacological interest, 4(5)-aryl-, 4,5-diaryl- and 4,5- diaryl-1-methyl-1H-imidazoles, 2-arylbenzothiazoles and 2-arylbenzimidazoles, including bioactive compounds or their precursors, and 2,4(5)-diaryl-1H-imidazoles is also disclosed. Finally, this account illustrates the results of an attempt to optimize a protocol for the direct C-2 arylation of 1H-indole, which enabled the development of a new, convenient and functional group-tolerant version of the Ullmann reaction for the Cu-mediated highly regioselective N-arylation of 1Hindole derivatives and 9H-carbazole.