Highly selective synthesis of 4(5)-aryl-, 2,4(5)-diaryl-, and 4,5-diaryl-1H-imidazoles via Pd-catalyzed direct C-5 arylation of 1-benzyl-1H-imidazole

Switching the Regioselectivity of Direct C–H Arylation of 1,3‐Dimethyluracil

“…While the reactions in the absence of CuI presumably proceed through the CMD mechanism [6] and thus follow the regioselectivity of electrophilic substitution (position 5), the reactions in the presence of CuI most likely proceed through cupration [7] of the heterocycle in the position of the more acidic H (position 6). The reaction in the absence of a Pd catalyst, which proceeds through an Ullmann coupling, is less efficient (but more selective) than reactions in the presence of Pd(OAc) 2 and ligand.…”

“…Extensive research has resulted in the development of efficient methodologies for C-H arylation of diverse aromatics and heterocycles. [5][6][7][8] Although a number of transition-metal complexes were used as catalysts, Pd complexes are the most versatile catalysts, successful in most cases. The reactions are performed either in the presence or in the absence of Cu I salts.…”

“…The Cu-free reactions were proved to proceed by a concerted metalationdeprotonation (CMD) mechanism, [6] which consists of the oxidative addition of the aryl halide to the Pd catalyst and attack of the resulting complex at the arene C-H bond with the assistance of a base to simultaneously cleave the C-H bond and form a C-Pd bond, followed by reductive elimination to afford the biaryl product. On the other hand, in several Cu-mediated reactions, direct metalation of the arene C-H bond by a base and copper salt was observed, [7] [a] Institute of Organic Chemistry and which generated an aryl cuprate that then underwent crosscoupling with an aryl halide (either Pd-catalyzed or noncatalyzed Ullmann type coupling). While electron-rich heterocycles are usually excellent substrates for C-H arylation, electron-poor heterocycles (i.e.…”

Mechanistic Elucidation of the Arylation of Non-Spectator N-Heterocyclic Carbenes at Copper Using a Combined Experimental and Computational Approach

“…Our findings may also suggest a pathway for catalyst deactivation for Cu I -NHCs as catalysts in the presence of water, and offer a reason to why high catalyst loadings or stoichiometric quantities are often necessary. [4][5][6][7][8][9][10][11][12][13][14]18 Cu I -NHC complexes 8 and 9 were prepared by reaction of the corresponding imidazolium salts with Cu 2 O in anhydrous DCM (both formed in quantitative yield). Single crystals of complex 8 suitable for X-ray diffraction analysis were grown via the vapor diffusion of diethyl ether into a solution of the product in dichloromethane.…”

“…[6][7][8][9][10][11][12] Adenosine can be functionalized using a similar route, to give 8-aryladenosine (Scheme 1b). 13,14 The functionalization of a benzimidazole to give a 2-arylbenzimidazole has been shown to proceed in the absence of Pd and using stoichiometric quantities of CuI, though higher reaction temperatures were employed in this reaction (Scheme 1c).…”