Reductive Ring Cleavage of Nonconjugated Δ^²-Isoxazolines to β-Hydroxy Ketones with Aluminum and Copper(II) Chloride

Abstract

A facile, economic, and efficient protocol for the reduction of nonconjugated Δ^²-isoxazolines to the corresponding β-hydroxy ketones using Al/CuCl₂ as the reducing agent has been developed. The method is both rapid and complete requiring less than ten minutes to attain total ring cleavage. This is the first example of using an in situ prepared Al/Cu couple in organic synthesis.

Key words

reduction - isoxazolines - β-hydroxyketones - aluminum/copper couple

References and Notes

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15

Typical Procedure for the Reductive Cleavage of 3,5-Disubstituted 4,5-Dihydroisoxazoles 1 To the mixture of the corresponding 3,5-disubstituted 4,5-dihydroisoxazole (1, 1 mmol) and Al dust (0.81 g, 30 mmol) in MeOH (5 mL) a solution of CuCl₂×2H₂O (1.75 g, 10 mmol) in H₂O (5 mL) was added dropwise under vigorous stirring. After the evolution of hydrogen and full consumption of the starting material (observed by TLC, approximately after 5-10 min), the mixture was diluted with H₂O (30 mL), and the product was extracted with CHCl₃ (2 ×30 mL). The organic layer was dried over Na₂SO₄, evaporated under the reduced pressure, and the residue purified by column chromatography to give 2.
Analytical Data for 5-Hydroxy-7-tridecanone (2a)
Yield: 84%; colorless oil. IR (KBr): ν_max = 3410 (OH), 1706 (C=O) cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 0.88 (3 H, t, J = 7.5 Hz, CH₃), 0.91 (3 H, t, J = 7.5 Hz, CH₃), 1.28-1.60 (14 H, m, 7 CH₂), 2.43 [2 H, t, J = 7.5 Hz, C(8)H₂], 2.48-2.54 [1 H, m, C(6)H], 2.57-2.64 [1 H, m, C(6)H], 3.03 (1 H, br s, OH), 3.99-4.07 [1 H, m, C(5)H] ppm. ^¹³C NMR (75 Hz, CDCl₃): δ = 13.8 (CH₃), 13.9 (CH₃), 22.4, 22.6, 23.5, 27.6, 28.7, 31.5, 36.1 (C-4), 43.6 (C-8), 48.9 (C-6), 67.5 (C-5), 212.6 (C-7) ppm. Anal. Calcd for C₁₃H₂₆O₂: C, 72.84; H, 12.23. Found: C, 73.00; H, 12.19.
Compounds 1-4 were also fully characterized by IR, ^¹H NMR, ^¹³C NMR spectroscopic and microanalytical data, and data for known compounds are in agreement with published data.