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

Herein, a formal highly enantioselective organocatalyzed [3+2] cycloaddition of furanone derivatives and azomethine ylides is presented. The success of this reaction resides in an intramolecular hydrogen bond activation through an o-hydroxy group at 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 to a highly efficient kinetic resolution of butenolides, achieving selectivity factors above 200. Using this methodology, furan-2(5H)-ones as well as furo[3,4-c]pyrrolidinones were obtained with high enantioselectivities. Quantum chemistry calculations reveal the crucial role of hydrogen bond formed between the catalyst donor-units and the two reagents, which modify their arrangement and promote effective facial discrimination resulting in a highly selective kinetic resolution. In addition, further applicability of the kinetic resolution process is shownPID2019-110091GB-I00, PID2021-122299NB-I00, TED2021-130470B-I00, TED2021-129999B-C32, “Comunidad de Madrid” for European Structural Funds (S2018/NMT-4367) and (Y2020/NMT6469), CEX2018-000805-