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Updated: Jun 22, 2025

Development of Heterogeneous Enantioselective Catalysts using Chiral Metal-Organic Frameworks MOFs
Published on: January 17, 2020
Computational Studies of Reactions of 1,2,4,5-Tetrazines with Enamines in MeOH and HFIP
Pengchen Ma1,2, Dennis Svatunek2,3, Zixi Zhu4
1Department of Chemistry, School of Chemistry, Xi'an Key Laboratory of Sustainable Energy Material Chemistry and Engineering Research Center of Energy Storage Materials and Devices, Ministry of Education, Xi'an Jiaotong University, Xi'an 710049, China.
Abstract:
The reaction between 1,2,4,5-tetrazines and alkenes in polar solvents proceeds through a Diels-Alder cycloaddition along the C-C axis (C3/C6 cycloaddition) of the tetrazine, followed by dinitrogen loss. By contrast, the reactions of 1,2,4,5-tetrazines with enamines in hexafluoroisopropanol (HFIP) give 1,2,4-triazine products stemming from a formal Diels-Alder addition across the N-N axis (N1/N4 cycloaddition). We explored the mechanism of this interesting solvent effect through DFT calculations in detail and revealed a novel reaction pathway characterized by C-N bond formation, deprotonation, and a 3,3-sigmatropic rearrangement. The participation of an HFIP molecule was found to be crucial to the N1/N4 selectivity over C3/C6 due to the more favored initial C-N bond formation than C-C bond formation.
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