“…Sauer’s pioneering studies on the synthesis and reactivities of 1,2,4,5-tetrazines with many dienophiles have provided inspiration for the design of a variety of reactions in bioorthogonal chemistry. , Sauer’s detailed reports on the synthesis and reactivities of substituted cyclopentadienes, however, have gone relatively unrecognized. , The highly reactive, self-orthogonal, and ambiphilic properties of the tetrachlorocyclopentadiene ketal (TCK) shown in Scheme and described by Sauer attracted our attention to it as a potential bioorthogonal diene. , Ambiphilic molecules can react as electrophiles or nucleophiles, depending on the reaction partner. TCK, being ambiphilic, is able to react with both electron-deficient dienophiles, such as maleic anhydride, and electron-rich dienophiles, such as (1 Z ,5 Z )-cycloocta-1,5-diene .…”