Direct Access to Fused Salicylaldehydes and Salicylketones from Tetraynes

Abstract

A facile method for the synthesis of fused, multifunctionalized salicylaldehydes and salicylketones by a one-pot, three-step cascade hexadehydro-Diels-Alder (HDDA) reaction of tetraynes followed by an intermolecular aldehyde/ketone reaction and hydroxylation is reported. Target compounds were prepared by the condensation of malonates with 3-bromo-1-propyne, and the resulting 2,2-di(1-propyn-3-yl)malonates underwent cross-coupling with phenylethynyl bromides to afford 2,2-di(5-phenyl-2,4-pentadiynyl)malonates, which underwent intramolecular cyclization to produce bicyclic salicylaldehydes. The overall transformation involves the formation of four new C-C bonds and one new C_aryl -O bond through both intramolecular and intermolecular reactions. The reaction is easy to perform, proceeds under mild conditions, and exhibits excellent regioselectivity. Water, a simple and readily available reagent, was employed as the OH source. A plausible reaction mechanism is proposed for this new annulation based on isotopic substitution experiments.

Keywords: condensed benzenoid compounds; cross-coupling; cyclization; hexadehydro-Diels-Alder reaction; salicylaldehyde derivatives.