Enantioselective Desymmetrization of 1,4-Dihydropyridines by Oxidative NHC Catalysis |
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| Authors: | Dr. Graziano Di Carmine Dr. Daniele Ragno Arianna Brandolese Prof. Olga Bortolini Daniel Pecorari Dr. Federica Sabuzi Prof. Andrea Mazzanti Prof. Alessandro Massi |
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| Affiliation: | 1. Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Via L. Borsari 46, I-44121 Ferrara, Italy;2. Department of Industrial Chemistry “Toso Montanari”, University of Bologna, V. Risorgimento 4, I-40136 Bologna, Italy;3. Department of Chemical Science and Technologies, University of Roma Tor Vergata, V. Ricerca Scientifica, I-00131 Roma, Italy |
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| Abstract: | The unprecedented desymmetrization of prochiral dialdehydes catalyzed by N-heterocyclic carbenes under oxidative conditions was applied to the highly enantioselective synthesis of 1,4-dihydropyridines (DHPs) starting from 3,5-dicarbaldehyde substrates. Synthetic elaboration of the resulting 5-formyl-1,4-DHP-3-carboxylates allowed for access to the class of pharmaceutically relevant 1,4-DHP-3,5-dicarboxylates (Hantzsch esters). DFT calculations suggested that the enantioselectivity of the process is determined by the transition state involving the oxidation of the Breslow intermediate by the external quinone oxidant. |
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| Keywords: | carbenes desymmetrization density functional calculations dihydropyridines organocatalysis |
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