Synthesis of 1-Aminoisochromenes through reactions of 2-alkynylbenzaldehydes with electron-poor anilines promoted by [Ag(PcL)] catalysts

Isochromene is an interesting oxygen-containing heterocycle characterizing different synthetic bioactive molecules and natural products. The isochromene core can be synthetized exploiting a regioselective 6-endo-dig domino approach starting from 2-alkynylbenzaldehydes and suitable nucleophiles, under transition metal catalysis, able to activate the triple bond. Most employed nucleophiles are oxygen- and carbon-based compounds, otherwise nitrogen-containing nucleophiles usually bring to the formation of isoquinoline derivatives, through the formation of the corresponding imine intermediate. Herein we report the first synthesis of 1-amino substituted isochromene derivatives starting from different 2-alkynylbenzaldehydes exploiting the features of electron-poor anilines and PcL silver complex catalysis. A series of 1-arylaminoisochromene was prepared, differently substituted in 3 position with alkyl, cycloalkyl, aryl or heteroaryl moiety. Reaction conditions, scope and limitation or the approach and a plausible mechanism of the reaction will be presented and discussed.