Peroxycarbenium Ions as the “Gatekeepers” in Reaction Design: Assistance from Inverse Alpha‐Effect in Three‐Component β‐Alkoxy‐β‐peroxylactones Synthesis

• Published in: Chemistry : a European journal 2019-11, Vol.25 (63), p.14460-14468
• Main Authors: Vil', Vera A., Barsegyan, Yana A., Barsukov, Denis V., Korlyukov, Alexander A., Alabugin, Igor V., Terent'ev, Alexander O.
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohols; anomeric effects; Carbonyl compounds; Carbonyls; Cations; Chemistry; Computer applications; Condensates; Hydrogen peroxide; Intermediates; Ketoesters; Organic chemistry; Organic peroxides; Oxidation; Peroxidation; Peroxides; peroxycarbenium ion; stereoelectronic effects; Synthesis
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201903752

Stereoelectronic interactions control reactivity of peroxycarbenium cations, the key intermediates in (per)oxidation chemistry. Computational analysis suggests that alcohol involvement as a third component in the carbonyl/peroxide reactions remained invisible due to the absence of sufficiently deep kinetic traps needed to prevent the escape of mixed alcohol/peroxide products to the more stable bisperoxides. Synthesis of β‐alkoxy‐β‐peroxylactones, a new type of organic peroxides, was accomplished by interrupting a thermodynamically driven peroxidation cascade. The higher energy β‐alkoxy‐β‐peroxylactones do not transform into the more stable bisperoxides due to the stereoelectronically imposed instability of a cyclic peroxycarbenium intermediate as a consequence of amplified inverse alpha‐effect. The practical consequence of this fundamental finding is the first three‐component cyclization/condensation of β‐ketoesters, H2O2, and alcohols that provides β‐alkoxy‐β‐peroxylactones in 15–80 % yields. The use of an amplified inverse alpha‐effect for interrupting a cascade peroxidation process in a three‐component synthesis of β‐alkoxy‐β‐peroxylactones from β‐ketoesters, hydrogen peroxide and alcohols was developed.