Synthesis of 2-Isoxazoline N-Oxides by Copper-Mediated Radical Annulation of Alkenes with α-Nitrobenzyl Bromides

Abstract

Copper-mediated [3 + 2] annulation of alkenes with α-nitrobenzyl bromides has been developed. The reaction is promoted simply by a copper salt to produce the corresponding 2-isoxazoline N-oxides with perfect regioselectivity. The present method can be conducted under mild conditions, affording a diverse array of 2-isoxazoline N-oxides. The obtained products can readily be converted to the related heterocycles such as 2-isoxazoline and isoxazole. A radical-polar crossover pathway initiated by single-electron transfer from nitronate to a copper salt is proposed.

Kupfer(I) Photokatalysierte Bromnitroalkylierung von Olefinen: Hinweise für effizienten Inner‐Sphären Mechanismus

“…Tatsächlich hatten Iwasaki et al. bereits gezeigt, dass die thermische Reaktion zwischen 1 e (R=Ph) und 2 a , initiiert durch Cu(OH) 2 (50 Mol‐%), ausschließlich zu Isoxazolin‐ N ‐Oxid 3 in 84 %iger Ausbeute führt [6c] …”

Five-Membered Hetarene N-Oxides: Recent Advances in Synthesis and Reactivity

“…Overall, these two complementary approaches enable a direct formation of a wide array of isoxazoline N-oxides 20 from readily available starting materials. 20…”

Intramolecular Radical Oxygen-Transfer Reactions Using Nitroarenes

“…19 Moreover, Ooi and Nishihara showed that C-radicals can cyclize onto the nitro functionality in nitroalkenes, leading to persistent nitroxyl radicals which can either be oxidized or reduced (see Scheme 1C). 20,21 It is important to note that secondary and tertiary nitroalkanes have been successfully used as C-radical precursors by Ono and others using tin hydrides as chain reductants. 22−24 However, in these cases, the actual O-transfer process to the chain carrying tin radical is not of relevance in the current context, as the translocated O-atom does not appear in the product structure.…”

“…Indeed, such oxygenations have been scarcely reported, with only few contributions made by Rovis, Chi and our group. ,− Motivated by earlier findings on their photochemistry, nitroarenes have recently also been employed as ozone substitutes in the “ozonolysis” of alkenes. , Related to this reactivity, the direct photoexcitation of nitroarenes has also been used for the anaerobic C–H oxidation in alkanes . Moreover, Ooi and Nishihara showed that C-radicals can cyclize onto the nitro functionality in nitroalkenes, leading to persistent nitroxyl radicals which can either be oxidized or reduced (see Scheme C). , It is important to note that secondary and tertiary nitroalkanes have been successfully used as C-radical precursors by Ono and others using tin hydrides as chain reductants. − However, in these cases, the actual O-transfer process to the chain carrying tin radical is not of relevance in the current context, as the translocated O-atom does not appear in the product structure. Combining all findings on the radical reactivity of nitro groups, intramolecular oxygen atom transfer from a nitro functionality should be feasible, if buildup of intermediate nitroso arenes can be somehow circumvented.…”