Synthesis of Imidazo[2,1-a]isoindolones via Rearrangement and Tandem Cyclization of Amino-Acid-Based N-Phenacyl-2-cyano-4-nitrobenzensulfonamides.

Abstract

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.