Bio-orthogonal tetrazine click reactions have recently attracted significant interest for applications spanning biological imaging, cancer targeting, and biomaterials science. Here, we report a simple and efficient two-step scheme for the synthesis of an asymmetric tetrazine molecule containing a carboxylic acid handle for subsequent macromolecular conjugation. Yields as high as 75% were achieved using as little as 0.005 equiv of nickel triflate catalyst, which is a significant improvement over previous methodologies. © 2013 Elsevier Ltd. All rights reserved.
Alge, D. L., Donohue, D. F., & Anseth, K. S. (2013). Facile and efficient Lewis acid catalyzed synthesis of an asymmetric tetrazine useful for bio-orthogonal click chemistry applications. Tetrahedron Letters, 54(41), 5639–5641. https://doi.org/10.1016/j.tetlet.2013.08.010