Intramolecular hydrogen bond activation for kinetic resolution of furanone derivatives by an organocatalyzed [3+2] asymmetric cycloaddition

Abstract

Herein, a formal highly enantioselectiveorganocatalyzed [3+2] cycloaddition of 5-methoxy-2(5H)-furanonesand derivatives, andazomethine ylides is presented. The success of this reaction resides in anintramolecular hydrogen bond activation through an o-hydroxy group at aromatic ring of the imine, allowing theformation of highly multifunctional bicyclic adducts with five stereogeniccenters in a stereocontrolled manner. Furthermore, the reaction is paired to ahighly efficient kinetic resolution of butenolides, achieving selectivityfactors above 200. Using this methodology, 2-(5H)-furanones as well as furo[3,4-c]pyrrolidinoneswere obtained with high enantioselectivities. Quantum chemistry calculationsreveal the crucial role of hydrogen bond formed between the catalystdonor-units and the two reagents, which modify their arrangement and promoteeffective facial discrimination resulting in a highly selective kineticresolution. In addition, further applicability of the kinetic resolutionprocess is shown.