Activation of O‑Electrophiles via Structural and Solvent Effects: SN2@O Reaction of Cyclic Diacyl Peroxides with Enol Acetates

• Published in: Journal of organic chemistry Vol. 87; no. 21; pp. 13980 - 13989
• Main Authors: Vil’, Vera A., Gorlov, Evgenii S., Shuingalieva, Diana V., Kunitsyn, Artem Yu, Krivoshchapov, Nikolai V., Medvedev, Michael G., Alabugin, Igor V., Terent’ev, Alexander O.
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.11.2022; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; MOLECULAR-ORBITAL METHODS; NUCLEOPHILIC-SUBSTITUTION; PHTHALOYL PEROXIDE; AUGMENTED BASIS-SETS; BETA-KETO-ESTERS; FLUORINATED ALCOHOLS; DENSITY-FUNCTIONAL THEORY; ENANTIOSELECTIVE ALPHA-HYDROXYLATION; ASYMMETRIC OXIDATION; SYN-DIHYDROXYLATION
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/acs.joc.2c01634

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 (SN2) reaction at oxygen (SN2@O). CF3CH2OH has a dual role in assisting in both steps of the reaction cascade: it lowers the energy of the SN2@O activation step by hydrogen bonding to a remote carbonyl and promotes the deacylation of the cationic intermediate.