Lithiation-Functionalisation of Triazoles Bearing Electron-Withdrawing N-Substituents: Challenges and Solutions** |
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Authors: | Frances E. Bugden Dr. Guy J. Clarkson Dr. Mark D. Greenhalgh |
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Affiliation: | Department of Chemistry, The University of Warwick, Coventry, CV4 7AL UK |
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Abstract: | The regioselective lithiation of 1,2,3-triazoles provides an opportunity to introduce additional functionality, however this simple functionalisation strategy using triazoles bearing electron-withdrawing N-substituents has not been investigated until now. Herein, we demonstrate that the lithiated triazole intermediates can readily decompose, even at −78 °C. In addition, lithiation-deuteration studies reveal lithiation can take place competitively on both the triazole and the electron-withdrawn aryl ring. Careful control of reaction conditions is therefore required to i) minimise decomposition pathways; and ii) facilitate regioselective functionalisation of the triazole. |
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Keywords: | deuterium fluorine heterocycles lithiation substituent effects |
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