Bioorthogonal Cycloadditions of C3‐Trifluoromethylated 1,2,4‐Triazines with trans‐Cyclooctenes

1,2,4-triazines are a valuable class of heterodienes that can be employed in inverse electron-demand Diels-Alder reactions. However, their broader application in bioorthogonal chemistry is limited due to their low reactivity. This article focuses on 3-(trifluoromethyl)-1,2,4-triazines, which can be efficiently prepared in a one-pot reaction from NH-1,2,3-triazoles. These triazines are highly reactive in reactions with strained cyclooctenes, giving second-order rate constants as high as 230 M