Domino reactions in water: diastereoselective synthesis of densely functionalized indolyldihydrofuran derivatives

A library of trans-5-aroyl-2-(indol-3-yl)-4-aryl-4,5-dihydrofuran-3-carbonitriles was diastereoselectively synthesized in excellent yields from the reaction of 2-(3-indolylcarbonyl)-3-aryl-2-propenenitriles with (2-aryl-2-oxoethyl)pyridinium bromides in the presence of triethylamine via a simple, user-friendly domino process carried out in water. Extraction and chromatographic steps were avoided, since the final products could be simply filtered from the aqueous reaction medium and recrystallized. This one-pot transformation generates one C C and one C O bond and presumably proceeds by a domino sequence involving the generation of a pyridinium ylide, a Michael addition and a final annulation via intramolecular nucleophilic substitution.