Acidity Controlled Formal Nucleophilic Substitution of Hydrofluoroolefin-Based Iodonium Salt with O-nucleophiles: Synthetic Application and Mechanistic Study.

ABSTRACT: The development and mechanistic investigation of a novel O-fluoroalkylation of phenol derivatives using a hypervalent fluoroalkyliodonium salt, derived from hydrofluoroolefin gas (HFO-1234yf) as bulk fluorous feedstock, is reported. Optimization of the reaction conditions enabled versatile and efficient synthetic applications, and the synthetic study revealed phenol acidity-dependent selectivity of the O-fluoroalkylation process. The mechanistic behavior of phenols was supported by both experimental studies and DFT calculations. As a result, we showed that more acidic phenols (pKa < 5) undergo direct O-alkylation, while reactions of the fluoroalkyliodonium salt involving less acidic phenol substrates proceed via a base-assisted chloride elimination and substitution pathway. Deuterium-label

SUBMITTER: Csenki JT 

PROVIDER: S-EPMC12510139 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature