Ytterbium triflate promoted solvent-free synthesis of 2-amino-4H-pyranes

Abstract

2-Amino-4H-pyrane derivatives are nowadays well recognized as valuable scaffold in drug discovery. In this manuscript a new and improved multicomponent process for the chemical synthesis of the title compounds is described. β-Dicarbonyl and activated cyanomethylene compounds, and aromatic, aliphatic or α,β-unsaturated aldehydes have been subjected to a three-component reaction under the catalysis of ytterbium triflate hydrate under solvent-free conditions at 50°C, and by application of microwaves and ultrasounds. Of the three methodologies employed, the reaction in neat performed in a flask with magnetic stirring proved to be by far the most efficient, providing the desired adducts in very good yields (85–91%). The experimental protocol set-up in this study was applied without significant differences in terms of yields to aromatic aldehydes having electron withdrawing or electron-donating substituents, as well as to aliphatic and α,β-unsaturated ones. Moreover ytterbium triflate has been easily recovered from each reaction media and reused without appreciable loss of its catalytic activity.