A Palladium Iodide-Catalyzed Oxidative Aminocarbonylation–Heterocyclization Approach to Functionalized Benzimidazoimidazoles

Abstract

A novel carbonylative approach to the synthesis of functionalized 1H-benzo[d]imidazo[1,2-a]imidazoles is presented. The method consists of the oxidative aminocarbonylation of N-substituted-1-(prop-2-yn-1-yl)-1H-benzo[d]imidazol-2-amines, carried out in the presence of secondary nucleophilic amines, to give the corresponding alkynylamide intermediates, followed by in situ conjugated addition and double-bond isomerization, to give 2-(1-alkyl-1H-benzo[d]imidazo[1,2-a]imidazol-2-yl)acetamides. Products were obtained in good to excellent yields (64-96%) and high turnover numbers (192-288 mol of product per mol of catalyst) under relatively mild conditions (100 °C under 20 atm of a 4:1 mixture of CO-air), using a simple catalytic system, consisting of PdI (0.33 mol %) in conjunction with KI (0.33 equiv).

PdI2-Based Catalysis for Carbonylation Reactions: A Personal Account

“…Propynylbenzimidazolamines, already successfully employed for the synthesis of benzimidazopyrimidinones under oxidative alkoxycarbonylation conditions (Scheme 6, Section 2.2) [43], were also used as substrates under aminocarbonylation conditions, to produce benzimidazoimidazoles in good to excellent yields after a final isomerization process (Scheme 19) [79]. In a similar way, benzimidazothiazoles were synthesized from propynylsulfanylbenzimidazoles, obtained in situ from the corresponding benzimidazolium bromide salts (Scheme 20) [80].…”

“…Catalysts 2019, 9, Scheme 19. Synthesis of benzimidazoimidazoles by sequential oxidative PdI2-catalyzed aminocarbonylation-N-cyclization-isomerization of propynylbenzimidazolamines [79].…”

“…Synthesis of benzimidazoimidazoles by sequential oxidative PdI 2 -catalyzed aminocarbonylation-N-cyclization-isomerization of propynylbenzimidazolamines [79]. In some cases, and under suitable conditions, the initial PdI2-catalyzed aminocarbonylation of the terminal triple bond is followed by PdI2-catalyzed cyclocarbonylation through the concatenation of two different catalytic cycles, both catalyzed by the same species (auto-tandem catalysis).…”

“…(a) Synthesis of isoindolinones by sequential PdI2-catalyzed oxidative aminocarbonylation-N-cyclization of 2-ethynylbenzamides [61,77] and (b) their use for the preparation of spiro[isoindole-1,5′-isoxazolidin]-3(2H)ones with antitumor activity[78]. Synthesis of benzimidazoimidazoles by sequential oxidative PdI2-catalyzed aminocarbonylation-N-cyclization-isomerization of propynylbenzimidazolamines[79].Scheme 20. Synthesis of benzimidazothiazoles by sequential PdI2-catalyzed oxidative aminocarbonylation-N-cyclization-isomerization of propynylsulfanylbenzimidazoles[80].Scheme 20.Synthesis of benzimidazothiazoles by sequential PdI 2 -catalyzed oxidative aminocarbonylation-N-cyclization-isomerization of propynylsulfanylbenzimidazoles[80].…”

A New Tool in the Quest for Biocompatible Phthalocyanines: Palladium Catalyzed Aminocarbonylation for Amide Substituted Phthalonitriles and Illustrative Phthalocyanines Thereof

“…Palladium-catalyzed carbonylation reactions were first described by Heck almost 40 years ago [38]. Since then, many developments have been reported [6,[39][40][41][42][43][44][45][46] and nowadays carbonylation has become an indispensable alternative to the classic organic synthesis of carbonyl compounds, including carboxylic acid derivatives (e.g., amides, esters) with valuable application in both industrial and fine chemistry. Among these reactions, aminocarbonylation [47][48][49][50], carried out using Ar-X substrates (X = I, Br, Cl, OTf, OTs, etc.…”