Q. Xiao, Wen‐Hua Wang, Gang Liu
Jul 27, 2009
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Chemistry
Abstract
A novel and straightforward method to construct 1H-benzo[d]imidazole was developed b means of Pd-catalyzed intramolecular C H activation starting from readily available N-phenylbenzimidamide. The detailed mechanism studies indicated that a palladacycle monomer or dimer is the key intermediate for this transformation and thiourea was first used to prompt the efficiency of C H activation. Much attention has been paid to C N formation in the past two decades. Many useful methods have been developed to construct C N bonds through transition-metal-catalyzed amination/amidation from aryl halides. Very recently, new methods have been developed to construct C N bonds intra/intermolecularly through direct aromatic C H functionalization. Among these investigations, Buchwald and co-workers pioneered studies to construct a carbazole core structure through Pd-catalyzed intramolecular C H activation. Shortly afterwards, Che, Yu, and co-workers reported the intermolecular C N formation through Pdor Cu-catalyzed C H functionalization, respectively. When we were preparing this manuscript, Buchwald and co-workers reported a novel Cu-catalyzed direct C H functionalization to produce benzimidazoles similar to our design. In their report, steric hindered benzimidamides showed the excellent reactivities to facilitate this transformation. Herein we report a new method to construct 1H-benzo[d]imidazole through Pd-catalyzed intramolecular C N formation, in which not only the substrate scope was widely extended, but also thiourea (tetramethylthiourea, TMTU) was introduced for the first time as an additive to promote the efficiency of the Pd catalysis for the direct C H transformation. 1H-benzo[d]imidazole (1 a) is a unique structural unit of many natural products and synthetic drugs. This scaffold can be obtained starting from benzene-1,2-diamine and its derivatives. Very recently, Ma and Buchwald made significant contributions to constructing this useful scaffold through Pdor Cu-catalyzed tandem reactions starting from amines and ortho-haloacetanilides, which are readily available through the developed highly selective halogenation of acetanilides. Undoubtedly, the most straightforward method to construct this scaffold is to construct C N bond directly through highly selective C H activation from the aniline derivatives (Scheme 1).