Palladium‐ and Copper‐Mediated Direct C‐2 Arylation of Azoles — Including Free (NH)‐Imidazole, ‐Benzimidazole and ‐Indole — Under Base‐Free and Ligandless Conditions

Abstract

The first palladium‐ and copper‐mediated C‐2 arylations of thiazole, oxazole, N‐methylimidazole and N‐arylimidazoles, as well as of free (NH)‐imidazole, ‐benzimidazole and ‐indole, with aryl iodides under ligandless and base‐free conditions are described. Complete selectivity has been achieved under these unprecedented conditions, which allow the use of substrates containing base‐sensitive groups, such the NH groups of imidazole, benzimidazole or indole, without their prior protection. No N‐arylation products were detected in the arylation of free (NH)‐imidazole, ‐benzimidazole and ‐indole. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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.…”

“…20 mins. The sample was returned to the glove-box, where PhI (14.7 mg, 0.0724 mmol, 8 L, 5 eq.) was added.…”

“…[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).…”

Direct Transition Metal Catalyzed Functionalization of Heteroaromatic Compounds

“…48,49 Under the unprecedented base-and ligand-free conditions, complete regioselectivity has been achieved. The protocol involved catalytic Pd(OAc) 2 and stoichiometric CuI in DMF.…”

Toward an Ideal Synthesis of (Bio)molecules through Direct Arene Assembling Reactions

“…Thiazole (42) was coupled with iodobenzene under Pd(OAc) 2 /CuI catalysis 22 to give 2-phenylthiazole (40) in 72% yield. Thereafter, palladium-catalyzed C4-selective CH arylation of 40 with p-tolylboronic acid (14b) was conducted under the influence of Pd(OAc) 2 /phen/ TEMPO/LiBF 4 to furnish the corresponding 2,4-diarylthiazole 41b in 75% yield with >95% regioselectivity.…”