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Keywords:

  • bioorthogonal synthesis;
  • cycloaddition;
  • heterocycles;
  • metal catalysis;
  • tetrazines
Thumbnail image of graphical abstract

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).