Computational studies on the Carboni-Lindsey reaction

Abstract The Carboni-Lindsey reaction between tetrazines and strained unsaturated hydrocarbons has in recent years become a useful tool in bioorthogonal chemistry for labelling biomolecules in vitro and in vivo. Here, we report computational studies on the mechanism of the Diels-Alder/Retro-Diels-Alder reaction between a commercially available tetrazine and norbornene. Isomerism of the reaction with a norbornene-amide relevant for applications in bioconjugation chemistry, as well as the role of protonation in the mechanism, is assessed.