Activation of O-Electrophiles via Structural and Solvent Effects: S N 2@O Reaction of Cyclic Diacyl Peroxides with Enol Acetates.

The reactions of O-electrophiles, such as organic peroxides, with carbon nucleophiles are an umpolung alternative to the common approaches to C-O bond formation. Nucleophilic substitution at the oxygen atom of cyclic diacyl peroxides by enol acetates with the following deacylation leads to α-acyloxyketones with an appended carboxylic acid in 28-87% yields. The effect of fluorinated alcohols on the oxidative functionalization of enol acetates by cyclic diacyl peroxides was studied experimentally and computationally. Computational analysis reveals that the key step proceeds as a direct substitution nucleophilic bimolecular (S N 2) reaction at oxygen (S N 2@O). CF 3 CH 2 OH has a dual role in assisting in both steps of the reaction cascade: it lowers the energy of the S N 2@O activation step by hydrogen bonding to a remote carbonyl and promotes the deacylation of the cationic intermediate.