Herein, we report an intermolecular anti-Markovnikov hydroetherification initiated through proton-coupled electron transfer (PCET). Though PCET has facilitated formation of alkoxy radicals, accessing the intermolecular reactivity of these intermediates remains challenging due to their inherent instability and kinetic facility of competitive unimolecular transformations such as β-scission and π-cyclization or preemptive reduction through electron transfer. To accelerate intermolecular trapping, nucleophilic olefins such as enoxysilanes and enamides were selected as bimolecular traps. To attenuate the off-target oxidation of these electron-rich alkenes, we designed a novel organophotocatalyst that undergoes stimulus-gated redox activation upon hydrogen bonding with alcohol substrates, deactivating the catalyst outside of these precursor complex associations. This species has enabled efficient intermolecular hydroetherification with alkoxy radical intermediates generated directly from diverse alcohol precursors under mild conditions and with low catalyst loadings. Notably, alcohol substrates susceptible to 1,5-hydrogen atom abstraction, β-scission, and π-cyclization are shown to undergo intermolecular addition. Luminescence titration experiments and reactivity studies were performed to support a hydrogen bond-activated PCET mechanism.
Delgutte et al. (2026) studied this question.