Esters of amino acids were reacted with 2-cyano-4-nitrobenzenesulfonyl chloride or 2-cyano-4-(trifluoromethyl)benzenesulfonyl chloride and alkylated with various α-haloketones. The corresponding sulfonamides were heated in a solution of ammonium acetate, which yielded imidazo[2,1-a]isoindolones in one step. The key reaction was based on intramolecular C-arylation followed by spontaneous cycloaddition and cyclocondensation. Two approaches have been developed: (i) solid-phase synthesis starting from amino acids immobilized on Wang resin, which allows the rapid preparation of target compounds using the cyclative cleavage strategy, and (ii) traditional solution-phase synthesis using amino acid methyl esters as the starting materials. The advantages and drawbacks of both alternatives are compared.

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Immobilized l-glutamic acid β-methyl ester was sulfonylated with 4-nitrobenzenesulfonyl chloride and alkylated with various α-haloketones. The resulting sulfonamides were reacted with potassium trimethylsilanolate. Then, upon cleavage from the polymer support, tetrasubstituted pyridines were produced as the result of one-step C-arylation, aldol condensation, and oxidation. When cleavage from the resin occurred before the trimethylsilanolate treatment, C-arylation was followed by enamination, which yielded trisubstituted pyrazines. Through the developed protocols, targeted synthesis of novel heterocyclic derivatives was performed using mild reaction conditions and a number of readily available starting materials.

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