Ultrasound‐Promoted Radical Synthesis of 5‐Methylselanyl‐4,5‐dihydroisoxazoles

Abstract

The ultrasound-promoted synthesis of 5-methylselanyl-4,5-dihydroisoxazoles through the radical cyclization of unsaturated oximes with diaryl diselenides using Oxone® as an oxidant and ethanol as the solvent is described. The key step of the reaction is the ultrasound-initiated homolytic cleavage of KHSO 5 , leading to the formation of sulfate and hydroxyl radi- [a]

Dichalcogenides/Oxone®‐Mediated Cyclization of (Z)‐Chalcogenoenynes under Ultrasound Irradiation

“…Thus, based on the above observations and on previous reports involving electrophilic cyclization reactions, [70][71][72] the reactivity of Oxone ® [40,43,81] and reactions under ultrasonic irradiation, [77][78][79][80][81] a plausible mechanism for the formation of chalcogenophenes 7-9 from 1-3 is presented in Scheme 4.…”

“…When the reaction mixture was refluxed for 8 h, the expected product 7 a was isolated in 77 % yield. Then, encouraged by recent positive results described by our research group, [77][78][79][80][81] and interested in reducing the reaction time, the mixture was sonicated at 60 % of amplitude for 60 min, using an ultrasonic probe, obtaining the desired product 7 a in 78 % yield (Table 1, entry 1). Considering this yield as satisfactory, the influence of the solvent on the performance of the cyclization was investigated ( Table 1, entries 2-12).…”

“…Once formed, intermediate B is activated in the acidic medium to form the strongest electrophile B'. [40,43,81] Then, enynes 1, 2 or 3 react with A or B to form the chalcogenironium intermediate C, that after an intramolecular attack by the electron pair of the chalcogen, gives the chalcogenonium intermediate D. Finally, D suffers a nucleophilic attack by one of the nucleophilic species present in the reaction medium (SO 4 2À , HSO 4 À ) to form the desired products 7-9 (Scheme 4).…”

Oxime radicals: generation, properties and application in organic synthesis

“…Under ultrasound irradiation β,γ-unsaturated oximes 195 react with KHSO 5 •0.5KHSO 4 •0.5K 2 SO 4 and diselenides 196 to form isoxazolines 197 [157] (Scheme 68) The introduction of electron-withdrawing substituents (example 197b) into the benzene ring of diselenide leads to an increase in yield compared to the case of electron-donating substituents (example 197c). Dialkyl diselenides also undergo this transformation (example 197d).…”

“…However, control experiments allowed to suggest that the reaction can proceed by both radical and ionic mechanisms. The authors proposed that under ultrasonic stimulation the mechanism is predominantly radical, while under microwave conditions the ionic mechanism becomes significant [157].…”