Direct Access to Fused Salicylaldehydes and Salicylketones from Tetraynes

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 Caryl−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. Domino sequences: A convenient method for synthesizing multifunctionalized salicylaldehydes and salicylketones by the reaction of tetrayne systems with DMF or N,N‐dimethylacetamide is reported. The method involves a cascade hexadehydro‐Diels–Alder and [2+2] cycloaddition reaction, an intermolecular aldehyde/ketone reaction, and hydroxylation. The salicylaldehydes produced have multiple rings, complex and variable structures, and broad applicability in chemical and drug preparation.