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Synlett 2012(3): 381-384  
DOI: 10.1055/s-0031-1290310
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Reductive Ring Cleavage of Nonconjugated Δ²-Isoxazolines to β-Hydroxy Ketones with Aluminum and Copper(II) Chloride

Ieva Karpaviciene, Ringaile Lapinskaite, Algirdas Brukstus, Inga Cikotiene*
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania
Fax: +370(5)2330987; e-Mail: inga.cikotiene@chf.vu.lt;
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Publication History

Received 6 October 2011
Publication Date:
19 January 2012 (online)

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Abstract

A facile, economic, and efficient protocol for the reduction of nonconjugated Δ²-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

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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): νmax = 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.