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Synlett 2008(6): 919-923  
DOI: 10.1055/s-2008-1042906
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Access to Isoxazoles from Alkenes

Jianping Xu, Ashton T. Hamme II*
Department of Chemistry, Jackson State University, Jackson, MS 39217-0510, USA
Fax: +1(601)9793674; e-Mail: ashton.t.hamme@jsums.edu;
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Publikationsverlauf

Received 18 December 2007
Publikationsdatum:
11. März 2008 (online)

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Abstract

The direct regioselective synthesis of 3,5-disubstituted isoxazoles was achieved in one reaction vessel through a sequence of reactions involving the net bromination of an electron-deficient alkene, in situ generation of a nitrile oxide, 1,3-dipolar cycloaddition, and loss of HBr from an intermediate 5,5-disubstituted bromoisoxazoline. This one-pot process enables the synthesis of 3,5-disubstituted isoxazoles directly from electron-deficient alkenes thereby negating the isolation of the 1,1-disubstituted bromoalkene alkyne surrogate.

Key words

cycloadditions - heterocycles - tandem reactions - alkyne surrogate - dehydrohalogenation

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15

General Experimental Procedure
After the alkene (0.5 mmol) was dissolved in CH2Cl2 (15 mL), bromine (0.55 mmol) was added dropwise. After all of the alkene was completely consumed, as confirmed by TLC on silica gel (hexanes-EtOAc, 4:1), the hydroximoyl chloride (0.5 mmol) was added, and Et3N (1.2 mmol) was added shortly thereafter. The reaction mixture was stirred at r.t. until the disappearance of the bromoalkene, as verified by TLC on silica gel (hexanes-EtOAc, 4:1). The reaction mixture was washed with H2O (3 × 10 mL), and the organic layer was dried over anhyd Na2SO4. The crude products were purified by flash column chromatography over silica gel using hexanes-EtOAc (4:1) as the eluent system. This procedure provides pure isoxazole products for entries 1-15 in 58-97% yield.
Spectroscopic data for Entry 9, Table 1
Colorless solid (74 mg, 73%), mp 84-87 °C. IR (CaF2, CCl4): ν = 1696 cm-1. 1H NMR: δ = 3.89 (s, 3 H), 7.00 (d, J = 8.9 Hz, 2 H), 7.25 (s, 1 H), 7.79 (d, J = 8.9 Hz, 2 H), 10.02 (s, 1 H). 13C NMR: δ = 55.4, 106.4, 114.2 (2 C), 119.9, 128.3 (2 C), 161.5, 162.7, 165.9, 178.5. HRMS (EI): m/z calcd for C11H9NO3 [M+ + 1]: 203.0582; found: 203.0628. All spectroscopic and HRMS data were obtained for previously unreported compounds.