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

Abstract

Herein, a formal highly enantioselective organocatalyzed [3 + 2] cycloaddition of furanone derivatives and azomethine ylides is presented. The success of this reaction resides in intramolecular hydrogen bond activation through an o-hydroxy group at the aromatic ring of the imine, allowing the formation of highly multifunctional bicyclic adducts with five stereogenic centers in a stereocontrolled manner. Furthermore, the reaction is paired with a highly efficient kinetic resolution of butenolides, achieving selectivity factors above 200. Using this methodology, furan-2(5H)-ones and furo[3,4-c]pyrrolidinones were obtained with high enantioselectivities. Quantum chemistry calculations reveal the crucial role of the hydrogen bond formed between the catalyst donor-units and the two reactants, which modifies their arrangement and promotes effective facial discrimination resulting in a highly selective kinetic resolution. In addition, further applicability of the kinetic resolution process is shown.