4,5-Dihydroisoxazoles by Copper(II)-Catalysed Condensation of Primary Nitroalkanes with Dipolarophiles

Abstract

Primary aliphatic nitro compounds condense with substituted alkenes to give 4,5-dihydroisoxazoles under copper(II) acetate catalysis in the presence of tertiary amines. Apparently nitrile ­oxides are not intermediates, as no furoxans are detected in these ­reactions.

Key words

nitroalkanes - copper - catalysis - isoxazolines

References and Notes

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9

Typical Procedure for the Catalysed Condensation of 1-Nitropentane and Methyl Acrylate Copper(II) acetate (3.9 mg, 0.021 mmol) was treated with a solution of nitropentane (124 mg, 1.06 mmol), methyl acrylate (37 mg, 0.42 mmol), and 1-methylpiperidine (21 mg, 0.21 mmol) in CHCl₃ (1.4 mL) and the mixture magnetically stirred in a sealed vessel (Schlenk) at 60 °C. After 40 h the reaction mixture was concentrated and the residue dissolved in EtOAc (15 mL) and washed with 5% HCl (3 × 15 mL portions), sat. Na₂CO₃ (3 × 15 mL portions), and brine (3 × 15 mL portions). The organic layer was dried (Na₂SO₄), filtered, and concentrated. The residue was purified by chromatography on silica gel eluting first with hexane and then with hexane-Et₂O (4:3). The isoxazoline [R _f (hexane-Et₂O) = 0.22, 71 mg] was obtained as a clear oil in 90% yield.
Analytical Data
¹H NMR (400 MHz, CDCl₃): δ = 0.91 (t, J = 7.6 Hz, 3 H, CH ₃), 1.29-1.41 (m, 2 H, CH ₂CH₃), 1.48-1.59 (m, 2 H, CH ₂CH₂C-3), 2.35 (t, J = 8.0 Hz, 2 H, CH₂C-3), 3.19 (d, J = 9.0 Hz, 2 H, 4-H), 3.76 (s, 3 H, OCH₃), 4.96 (t, J = 9.0 Hz, 1 H, 5-H) ppm. ¹³C NMR (100.58 MHz, CDCl₃): δ = 13.6 (q, CH₃), 22.2 (t, CH₂CH₃), 26.8 (t, CH₂C-3), 28.3 (t, CH₂CH₂CH₃), 40.8 (t, C-4), 52.6 (q, OCH₃), 76.8 (d, C-5), 158.4 (s, C-3), 171.0 (s, C=O) ppm. MS (EI, 70 eV): m/z (%) = 185 (<1) [M]⁺, 143 (23), 126 (12) [M - CO₂Me]⁺, 98 (20), 57 (100). IR (CDCl₃): 1739 (C=O), 1622 (C=N) cm^-1. Anal. Calcd for C₉H₁₅NO₃ (185.22): C, 58.36; H, 8.16; N, 7.56. Found: C, 58.19; H, 8.43; N, 7.89.