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

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.