Water-controlled selectivity switch in a multicomponent reaction: One-pot stereoselective synthesis of (acyloxymethylidene)chromonyl-furochromones and amido-(acyloxymethylidene)chromones

Abstract

An efficient protocol for the selective synthesis of (acyloxymethylidene)chromonyl-furochromones or amido-(acyloxymethylidene)chromones via a water-controlled multicomponent cascade reaction of 3-formylchromones, linear carboxylic acid anhydrides, and alkyl isocanides in CH2Cl2 has been developed. (Acyloxymethylidene)chromonyl-furochromones were obtained in dry CH2Cl2; conversely, amido-(acyloxymethylidene)chromones were formed with wet CH2Cl2 (undried dichloromethane) as the solvent at room temperature. The reaction proceeds via the formation of a highly reactive O-acylatedoxonium intermediate, generated from the reaction between 3-formylchromones and linear carboxylic acid anhydrides. The subsequent trapping of the O-acylatedoxonium ion by aminofurochromone intermediate in situ generated by cycloaddition reaction of alkyl isocyanide and the second equivalent of 3-formylchromone in dry CH2Cl2, would give (acyloxymethylidene)chromonyl-furochromones in excellent diastereoselectivity and yields. Alternatively, O-acylatedoxonium intermediate could be also regioselectively trapped by α-addition of alkyl isocyanides in wet CH2Cl2 to provide amido-(acyloxymethylidene)chromones in good yields.