Synthetic and mechanistic studies of the multicomponent reaction of 2-(phenylethynyl)benzaldehyde, primary amine and diphenylphosphine oxide†

Abstract

The synthesis of potentially biologically active phosphinoyl functionalized N-(2-(phenylethynyl)benzyl)amine, 1,2-dihydro-isoquinoline and 2H-isoindoline via a multicomponent reaction of 2-(phenylethynyl)benzaldehyde, amine and diphenylphosphine oxide is described for the first time. Depending on the catalyst and the conditions used, the same one-pot three-component reaction can selectively lead to the mentioned three different products. The formation of the cyclic products was investigated by a comprehensive catalyst screening, as well as by quantum chemical calculations. It was found that for the synthesis of phosphinoyl functionalized N-(2-(phenylethynyl)benzyl)amine, there is no need to use any catalyst. For the complete formation of isoquinoline ring containing phosphine oxide, zirconium(IV) chloride was the most efficient catalyst and 2H-isoindol-1-ylphosphine oxide was synthesized selectively by a silver acetate catalyst. Furthermore, dihydro-isoquinolin-1-ylphosphine oxide was converted into the thermodynamically more stable 2H-isoindol-1-ylphosphine oxide.