Generation of Iminoxyl Radicals by Photoredox Catalysis Enables Oxidant-Free Hydroxygenation of β,γ-Unsaturated Oximes

Abstract

A visible-light photocatalytic generation of iminoxyl radicals has been accomplished under oxidant-free conditions. This approach offers a mild, atom-economical, and redox-neutral synthesis of 5-methylisoxazolines through radical hydroxygenation of β,γ-unsaturated oximes in the absence of an additional hydrogen source.

Key words

oximes - hydroxygenation - isoxazolines - photoredox reaction - iminoxyl radical

• References and Notes

• 1a Krylov I. B, Paveliev SA, Budnikov AS, Terent’ev AO. Beilstein J. Org. Chem. 2020; 16: 1234
• 1b Liao J, Ouyang L, Jin Q, Zhang J, Luo R. Org. Biomol. Chem. 2020; 18: 4709
• 2a Han W.-J, Wang Y, Zhang J, Chen F, Zhou B, Han B. Org. Lett. 2018; 20: 2960
• 2b Liu R, Wei D, Han B, Yu W. ACS Catal. 2016; 6: 6525
• 2c Zhu L, Wang G, Guo Q, Xu Z, Zhang D, Wang R. Org. Lett. 2014; 16: 5390
• 2d Li X, Ding Y, Qian L, Gao Y, Wang X, Yan X, Xu X. J. Org. Chem. 2019; 84: 12656
• 3a Bell J. D, Murphy JA. Chem. Soc. Rev. 2021; 50: 9540
• 3b Yu X.-Y, Chen J.-R, Xiao W.-J. Chem. Rev. 2021; 121: 506
• 3c Romero N. A, Nicewicz DA. Chem. Rev. 2016; 116: 10075
• 3d Shaw M. H, Twilton J, MacMillan DW. C. J. Org. Chem. 2016; 81: 6898
• 4 Hu X.-Q, Chen J, Chen J.-R, Yan D.-M, Xiao W.-J. Chem. Eur. J. 2016; 22: 14141
• 5 Li W, Jia P, Han B, Li D, Yu W. Tetrahedron 2013; 69: 3274
• 6 Hu X.-Q, Feng G, Chen J.-R, Yan D.-M, Zhao Q.-Q, Wei Q, Xiao W.-J. Org. Biomol. Chem. 2015; 13: 3457
• 7 Isoxazolines 2a–r; General ProcedureA flame-dried 8 mL tube was charged with the appropriate oxime 1 (0.2 mmol), Na₂CO₃ (31.8 mg, 0.3 mmol), and fac-[Ir(ppy₃)] (2.6 mg, 0.004mmol) in anhyd CHCl₃ (2.5 mL) under Ar. The resulting mixture was degassed by bubbling with Ar and then stirred for 36 h at rt with irradiation by 460 nm blue LEDs. The mixture was extracted with EtOAc (3 × 15 mL), and the combined organic layers were washed with brine (10 mL), dried (Na₂SO₄), filtered, and concentrated in vacuo. When the solvent had been completely removed, the residue was purified by column chromatography (silica gel).5-Methyl-3-(4-tolyl)-4,5-dihydroisoxazole (2a)Brown solid; yield: 21.6 mg (65%); mp 41−42 °C; R_f = 0.38 (PE–EtOAc, 10:1). ¹H NMR (500 MHz, CDCl₃): δ = 7.71–7.59 (m, 2 H), 7.47–7.33 (m, 3 H), 4.94–4.82 (m, 1 H), 3.43 (dd, J = 16.3, 10.1 Hz, 1 H), 2.93 (dd, J = 16.3, 8.0 Hz, 1 H), 1.43 (d, J = 6.2 Hz, 3 H).
• 8 Hu X.-Q, Chen J.-R, Wei Q, Liu F.-L, Deng Q.-H, Beauchemin AM, Xiao W.-J. Angew. Chem. Int. Ed. 2014; 53: 12163