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.

中文翻译：

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1,2,4,5-四嗪与烯胺在 MeOH 和 HFIP 中反应的计算研究


1,2,4,5-四嗪和烯烃在极性溶剂中的反应通过沿四嗪的 C-C 轴（C3/C6 环加成）的 Diels-Alder 环加成反应进行，然后损失二氮。相比之下，1,2,4,5-四嗪与烯胺在六氟异丙醇 (HFIP) 中的反应产生 1,2,4-三嗪产物，该产物源自跨 N-N 轴的正式 Diels-Alder 加成（N1/N4 环加成） ）。我们通过 DFT 计算详细探索了这种有趣的溶剂效应的机制，并揭示了一种以 C-N 键形成、去质子化和 3,3-σ 重排为特征的新反应途径。发现 HFIP 分子的参与对于 N1/N4 相对于 C3/C6 的选择性至关重要，因为初始 C-N 键形成比 C-C 键形成更有利。