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.
Citation
Valle-Amores , M A , Feberero , C , Martin-Somer , A , Díaz-Tendero , S , Smith , A D , Fraile , A & Alemán , J 2023 , ' Intramolecular hydrogen bond activation for kinetic resolution of furanone derivatives by an organocatalyzed [3+2] asymmetric cycloaddition ' , Organic Chemistry Frontiers , vol. Advance article . https://doi.org/10.1039/D3QO01471A
Publication
Organic Chemistry Frontiers
Status
Peer reviewed
ISSN
2052-4129Type
Journal article
Description
This work was supported by Spanish Ministry of Science and Innovation (projects PID2019-110091GB-I00, PID2021-122299NB-I00 TED2021-130470B-I00, TED2021-129999B-C32), “Comunidad de Madrid” for European Structural Funds (S2018/NMT-4367) and proyectos sinérgicos I+D (Y2020/NMT-6469), and the “María de Maeztu” (CEX2018-000805-M) Program for Centers of Excellence in R&D. A.M.S. thanks the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with Universidad Autónoma de Madrid in the line Support to Young Researchers, in the context of the V PRICIT (SI3-PJI-2021-00463). C. F. thanks Ministerio de Universidades for a Margarita Salas grant.Collections
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