An efficient and mild oxidant for the synthesis of s-tetrazines

PhI(OAc)2 serves as a mild and effective oxidant for the synthesis of s-tetrazine derivatives—molecules of emerging significance to the field of bioorthogonal chemistry. This reagent serves as a complementary oxidant to harsher nitrous reagents. The use of PhI(OAc)2 improves the synthesis of 5-amino-di(pyridin-2-yl)-s-tetrazine, a molecule that has been broadly used for cellular imaging and nuclear medicine. The generality of PhI(OAc)2 as the oxidant for tetrazine synthesis is demonstrated for nine tetrazines in 75–98% yield.