Synthetic Approaches to Sterically Hindered N‐Arylimidazoles through Copper‐Catalyzed Coupling Reactions

Abstract

Optimization studies allowed the efficient synthesis of a simple structural motif based on meta‐bis(1‐imidazolyl)benzenes 1 through copper‐catalyzed coupling of 1,3‐diiodobenzene and imidazole under mild reaction conditions. This protocol was then used to prepare a representative sterically hindered N‐arylimidazole 2a, the most common structural motif among N‐heterocyclic carbenes (NHC). Having optimized the main variables governing CuI‐catalyzed imidazole N‐arylation, the first Ullmann‐type synthesis of N‐mesitylimidazole (2a) is reported. Moreover, the coupling between boronic acids as the aryl donor partners and either imidazole or benzimidazole was examined; in all cases the reactions proceeded in very low yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Transition metals in organic synthesis: Highlights for the year 2005

“…The addition of a small amount of water was found beneficial in some amidation reactions [529]. Palladium catalyzed the intermolecular N-arylation or N-alkenylation of primary and secondary amines [530,531], polyamines [532], imidazoles [533], benzophenone hydrazine [376], N,N-dialkylhydrazines [534], sulfoximines [535,536] in a synthesis of erogorgiaene [350], sulfamides [537], pyrroles and indoles [538], aziridines [539], zinc trimethylsilylamide, as an ammonia equivalent [540], of 15 N-labelled benzamide [541], ureas [542] and linear polyamines [543] using aryl halides or alkenyl triflates. This type of reaction using a 3,5-dibromopyridine and aza-substituted 1,n-diamines was used to prepare polyazamacrocycles [544].…”

Cross‐Coupling Reactions on Azoles with Two and More Heteroatoms

“…Aerobic conditions were required to ensure conversion to the desired products, as O 2 plays a crucial role in regenerating the active catalyst within the catalytic cycle. [73] Buchwald et al also describe the copper-diamine-complex-catalyzed Narylation of imidazoles and some other π-excessive nitrogen heterocycles (pyrroles, pyrazoles, indazoles, triazoles). [68][69][70][71] Scheme 29. In the course of the development of new bis(carbene) ligands for cross-coupling reactions, double copper-catalyzed C-N bond formation on 1,3-dibromobenzene (85) provided 1,1Ј-(1,3-phenylene)-bis(1H-imidazole) (86) in 77 % yield (Scheme 30).…”

“…[72] Recently, sterically demanding aryl iodides were applied in C-N bond formations with imidazole under mild reaction conditions. [73] Buchwald et al also describe the copper-diamine-complex-catalyzed Narylation of imidazoles and some other π-excessive nitrogen heterocycles (pyrroles, pyrazoles, indazoles, triazoles). [74] Scheme 30.…”

N‐Functionalization of Azoles through Coupling Reactions with Alkoxydienyl and Alkoxystyryl Boronic Esters

“…Moreover, simple diamine ligands for CuI have also been used for the arylation of indoles, [6] pyrroles, pyrazoles, indazoles, imidazoles, and triazoles. [7] Recent developments reported by Chan and Lam [8] have demonstrated that arylboronic acids can be effective as arylating agents when stoichiometric quantities of Cu(OAc) 2 are used; these experimental conditions have been applied to the arylation of azoles, [9] pyrrole and methyl indole-2-carboxylate derivatives, [10] sterically hindered imidazoles, [11] and electron-deficient pyrroles. [12] More recently, heteroarenes have been arylated with catalytic Cu(OAc) 2 in the presence of stoichiometric amounts of mild oxidizing agents, [13] while Collman [14] has reported the arylation of In contrast, there are fewer examples of C-N bond formation as a method for N-vinylation through the use of boronic acids or esters.…”