Ma Pengchen, Svatunek Dennis, Zhu Zixi, Boger Dale L, Duan Xin-Hua, Houk K N
Department 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.
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States.
J Am Chem Soc. 2024 Jul 10;146(27):18706-18713. doi: 10.1021/jacs.4c06067. Epub 2024 Jun 28.
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.
在极性溶剂中，1,2,4,5-四嗪与烯烃之间的反应通过沿着四嗪的C-C轴（C3/C6环加成）进行狄尔斯-阿尔德环加成反应，随后失去氮气。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，这是通过跨N-N轴的形式上的狄尔斯-阿尔德加成反应（N1/N4环加成）得到的。我们通过密度泛函理论（DFT）计算详细探索了这种有趣的溶剂效应的机理，并揭示了一种以C-N键形成、去质子化和3,3-σ迁移重排为特征的新型反应途径。由于初始C-N键形成比C-C键形成更有利，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。
