The bioorthogonal elimination of trans-cyclooctenes (TCO) triggered by click reaction with 1,2,4,5-tetrazines (Tz) has gained significant attention due to exceptional reaction kinetics and molecular versatility. As pioneered by Robillard et al., TCO modified with a carbamate moiety in an allylic position (release-TCO, rTCO) undergoes a 1,4-elimination upon inverse electron demand Diels-Alder (IEDDA) reaction with Tz and subsequent post-click tautomerization, ultimately leading to the click-triggered release of an amine or amino-functionalized molecule (click-torelease). To expand the scope of Tz as molecular scissors to the activation of caged alcohols and phenols, vinyl ethers have been introduced as bioorthogonal reactants (Fig. ), representing a strategy for the design of a variety of prodrugs, considering that OH-functionalized compounds account for a large number of FDA-approved small-molecule therapeutics. However, only limited second-order rate constants (k2) of less than 0.001 M -1 s -1 have been observed for the IEDDA reaction of vinyl ethers and Tz. Versteegen et al. have subsequently developed rTCO-ethers and rTCO-carbonates that react substantially faster with Tz (k2 >10 M -1 s -1 ), leading to clicktriggered release of alcohols and phenols (Fig. ). However, in the case of rTCO-ethers only slow elimination was observed, requiring >30 hours to obtain >80% of the released alcohol or phenol. While click-to-release of phenolic rTCO-carbonates was found to proceed significantly faster (80% after approx. 15 hours), these compounds were reported to degrade rapidly under biological conditions (complete hydrolysis after 5 hours in 50% mouse serum at 37 °C), impeding application of this strategy in the development of click-activatable prodrugs.