l-Proline-Catalysed One-Pot aza-Diels–Alder Reaction in Water: Regioselective Synthesis of Spiro(isoxazolo[5,4-b]pyridine-5,5′-pyrimidine) Derivatives

Abstract

A simple and efficient l-proline-catalysed synthesis of spiro(isoxazolo[5,4-b]pyridine-5,5′-pyrimidine) derivatives in water has been accomplished through a pseudo five-component one-pot domino aza-Diels–Alder reaction involving 3-amino crotanonitrile, hydroxylamine hydrochloride, aromatic aldehydes and barbituric acids. The main advantages of the present method are mild reaction conditions, modest purification process involving no chromatographic techniques and high yields. The protocol is a good alternative to prepare spiro derivatives with readily available starting materials, which makes the method highly attractive.