Metal-Catalyzed One-Pot Synthesis of Tetrazines Directly from Aliphatic Nitriles and Hydrazine


  • The authors gratefully acknowledge Ralph Mazitschek, Carlos Guerrero, and Scott Hilderbrand for helpful discussions. This material is based upon work supported in part by NIH grant K01EB010078, the University of California, San Diego, and the NSF under CHE-0741968.


original image

Paving the way: The lack of convenient synthetic methods is a significant roadblock to the broader use of 1,2,4,5-tetrazines in bioorthogonal chemistry and functional materials. Lewis acid metal catalysts—most notably divalent nickel and zinc salts—are described to catalyze the one-pot synthesis of 1,2,4,5-tetrazines directly from aliphatic nitriles (see scheme).