Synthesis of diverse spiroisoxazolidinohydantoins by totally regio- and diasteroselective 1,3-dipolar cycloadditions

Abstract

5-Carboxymethylene hydantoins have been synthesized in high yield and under very mild conditions (20 °C, dichloromethane) through a highly (often totally) regio- and diastereoselective domino process involving readily accessible carbodiimides and acetylenedicarboxylic acid monoesters. Such compounds could be considered very intriguing intermediates for the preparation of spirohydantoins and other hydantoin derivatives. For instance, they react smoothly with either acyclic and cyclic nitrones to form spiroisoxazolidinohydantoins in high yield and with total control of the regio- and diastereoselectivity. Starting from an enantiomerically pure chiral pyrroline nitrone, the reaction was also enantiospecific. Both processes have been studied in detail and the diastereoselectivities seen have been rationalized upon examination of the alternative transition states and by density functional theory calculations of the cycloaddition step.