Origin of Increased Reactivity in Rhenium-Mediated Cycloadditions of Tetrazines

Abstract

Pyridyl tetrazines coordinated to metals like rhenium have been shown to be more reactive in [4+2] cycloadditions than their uncomplexed counterparts. Using density functional theory (DFT) calculations, and in particular distortion/interaction and energy decomposition analysis, we analyze the factors that contribute to this increase in reactivity. 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 is 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 product. 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.

Origin of Increased Reactivity in Rhenium-Mediated Cycloadditions of Tetrazines

“…Here, we perform a computational analysis using distortion/interaction and energy decomposition analysis to unravel the underlying mechanisms that lead to the observed increase in reactivity. An initial version of this work was deposited in ChemRxiv on July 2, 2021 …”