Palladium-Catalyzed Carbonylative Synthesis of Functionalized Benzimidazopyrimidinones

Abstract

A new and convenient approach to functionalized benzimidazopyrimidinones is reported. It is based on a two-step procedure starting from readily available 1-(prop-2-yn-1-yl)-1H-benzo[d]imidazol-2-amines, consisting of a multicomponent palladium-catalyzed oxidative cyclocarbonylation–alkoxycarbonylation process, followed by base-promoted isomerization of the initially formed mixture of isomeric carbonylated products. Fair to good overall yields of the final alkyl 2-(2-oxo-1,2-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-3-yl)acetates are obtained, using different alcohols as solvent and nucleophile in the carbonylation step (carried out in the presence of 0.33–1 mol% PdI₂ in conjunction with 17–50 mol% KI, at 100 °C and under 20 atm of a 4:1 mixture of CO–air) and the corresponding sodium alkoxide as base in the subsequent isomerization step (carried out in the alcoholic solvent at room temperature). The structures of a representative substrate [N-benzyl-1-(prop-2-yn-1-yl)-1H-benzo[d]imidazol-2-amine] and a representative product [methyl 2-(1-isopentyl-2-oxo-1,2-dihydrobenzo-[4,5]imidazo[1,2-a]pyrimidin-3-yl)acetate] were confirmed by X-ray diffraction analysis.

Key words

benzimidazopyrimidinones - carbonylation - cyclization - cyclocarbonylation - heterocyclization - homogeneous catalysis - palladium

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