Urotropine-bromine promoted synthesis of functionalized oxaspirotricyclic furopyrimidines via a domino Knoevenagel condensation/Michael addition/α-bromination/Williamson cycloetherification sequence in water

An efficient, safe and facile route to functionalized spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine] derivatives has been developed by a one-pot pseudo three-component domino coupling of aromatic aldehydes and (thio)barbituric acids in the presence of urotropine-bromine (UB) complex in water at room temperature. The reaction sequence consists of an initial Knoevenagel condensation of aromatic aldehydes with (thio)barbituric acids, followed by Michael addition of the second equivalent of (thio)barbituric acid derivatives, and then UB-catalyzed Williamson cycloetherification to afford the products.