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

Abstract

The synthesis of potentionally biologically active phosphinoyl functionalized N‑(2‑(phenylethynyl)benzyl)amine, 1,2‑dihydro-isoquinoline and 2H‑isoindoline via 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 the 2H-isoindol-1-ylphosphine oxide was synthesized selectively by silver acetate catalyst. Furthermore, dihydro-isoquinolin-1-ylphosphine oxide was converted into the thermodynamically more stable 2H-isoindol-1-ylphosphine oxide.