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.