Origin of Increased Reactivity in Rhenium-Mediated Cycloadditions of Tetrazines



Pyridyl tetrazines coordinated to metals like rhenium have been shown to be more reactive in [4+2] cycloadditions than their un-complexed counterparts. Using density functional theory (DFT) calculations, and in particular distortion/interaction and energy de-composition analysis, we analyze the factors that contribute to this increase in selectivity. The reaction of the complexed tetrazine has a more favorable interaction energy compared to the uncomplexed tetrazine, and the main contributor to this favorable interaction energy an increase in orbital interactions through a lowering of the LUMO in the complexed tetrazine. Additionally, the high regioselectivity of the reaction is shown to be due to a greater degree of charge stabilization in the transition state leading to the major prod-uct. This study suggests that the energy of the FMOs is a good indicator of reactivity in these reactions, and the enhanced [4+2] reactivity upon complexation adds another tool to the toolbox of click reactions.


Supplementary material

Supporting information
Energies of all discussed structures, additional energy decomposition analysis and orbital energies
Cartesian Coordinates
Cartesian coordinates as *.xyz for all discussed structures.