Direct and Regioselective Introduction of Acetals into Imidazoles at the 2‐Position by an Iridium‐Catalyzed Reaction with Formates in the Presence of Hydrosilanes

Abstract

The iridium‐catalyzed reaction of imidazoles with formates in the presence of hydrosilanes as coreactants led to the production of 2‐[(alkoxy)(siloxy)methyl]imidazoles. Dimethyl acetylenedicarboxylate was the additive of choice for the reaction in terms of reaction efficiency. No reaction was observed in the absence of the hydrosilanes. Whereas substituents at the 1‐ and 5‐positions on the imidazole ring did not affect the reaction, substituents at the 4‐position greatly retarded the reaction. The regioselective reaction of 1‐methyl‐1,2,4‐triazole occurred at the carbon atom between the sp3 and sp2 nitrogen atoms of the ring but not between two sp2 nitrogen atoms. The products were converted into imidazole 2‐carbaldehydes by hydrolysis under acidic conditions.

Iridium-Catalyzed Direct Amidation of Imidazoles at the C-2 Position with Isocyanates in the Presence of Hydrosilanes Leading to Imidazole-2-Carboxamides

“…The reaction using 0.1 equivalent of HSiEt 2 Me resulted in a significant decrease in the product to 8% (entry 4). Other metal carbonyls, such as Mn 2 (CO) 10 , Fe 3 (CO) 12 , Ru 3 (CO) 12 , and Co 2 (CO) 8 , showed no catalytic activity for the present reaction. In our previous reports on the reaction with aldehydes 11 and formates, 12 the addition of a catalytic amount of DMAD, probably as a ligand, and not a hydrogen scavenger, was found to dramatically improve the product yields.…”

“…Other metal carbonyls, such as Mn 2 (CO) 10 , Fe 3 (CO) 12 , Ru 3 (CO) 12 , and Co 2 (CO) 8 , showed no catalytic activity for the present reaction. In our previous reports on the reaction with aldehydes 11 and formates, 12 the addition of a catalytic amount of DMAD, probably as a ligand, and not a hydrogen scavenger, was found to dramatically improve the product yields. On the other hand, the present reaction was not affected by the addition of DMAD, in terms of the product yield of 1a, although the reason for this difference is cur-rently unclear (entry 5).…”

“…11 Since that report, the direct introduction of mixed alkyl-silyl acetals into imidazole derivatives at the 2-position using formates appeared, one product of which was hydrolyzed under acidic conditions to form 2-formylimidazoles. 12 The addition of hydrosilanes was found to be crucial for both reactions to proceed. We report herein the direct C2functionalization of imidazoles with isocyanates 13 to give imidazole-2-carboxamides, catalyzed by Ir 4 (CO) 12 with a stoichiometric amount of hydrosilanes as a co-reactant (Scheme 1).…”

“…2 Only a limited number of reports have appeared on the introduction of carbonyl and the related groups into imidazole C-H bonds. 3 Our group developed the Ru 3 (CO) 12 -catalyzed regioselective acylation of an imidazole ring with CO and alkenes. 4 The direct C-H aroylation of imidazole derivatives at the 2-poition with CO and p-me-thoxyiodobenzene, catalyzed by a palladium complex, was reported.…”

“…9 Daugulis reported the selective, CuCN catalyzed C-H cyanation of imidazoles with NaCN in the presence of a strong base. 10 In 2002, we reported the regioselective C-H functionalization of imidazole derivatives with aldehydes at the C-2 position, catalyzed by Ir 4 (CO) 12 in the presence of hydrosilanes, leading to the production of 2-[2-(siloxy)alkyl]imidazoles. 11 Since that report, the direct introduction of mixed alkyl-silyl acetals into imidazole derivatives at the 2-position using formates appeared, one product of which was hydrolyzed under acidic conditions to form 2-formylimidazoles.…”