Tetrahydroquinolines by the multicomponent Povarov reaction in water: calix[n]arene-catalysed cascade process and mechanistic insights

Abstract

The catalyst p-sulfonic acid calix[4]arene was effectively used in the three-component Povarov reaction between aromatic anilines and two equivalents of 2,3-dihydrofuran to obtain furano[3,2-c]-1,2,3,4-tetrahydroquinolines. These reactions proceeded efficiently using water as a green solvent and nontoxic catalysts that could be efficiently reused; the reactions were metal-free and used only inexpensive and easily available compounds. Together with a simple workup procedure, these advantages make this protocol a very efficient and green alternative to the traditional methods for constructing tetrahydroquinoline structures, through the formation of two new C–C bonds and one C–N bond. Isotopic labelling experiments revealed the mechanism for the Povarov reactions, showing that the reaction proceeds through a sequence of steps via ionic intermediates, and the proposed reaction mechanism was validated.