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Synlett 2009(9): 1511-1513  
DOI: 10.1055/s-0029-1217182
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient and Convenient Protocol for Highly Regioselective Cleavage of Terminal Epoxides to β-Halohydrins

Tao Wang, Wen-Hao Ji, Zhong-Yu Xu, Bu-Bing Zeng*
School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. of China
Fax: +86(21)64253689; e-Mail: zengbb@ecust.edu.cn;
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Publikationsverlauf

Received 18 December 2008
Publikationsdatum:
13. Mai 2009 (online)

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Abstract

An efficient and facile strategy for the cleavage of terminal epoxides to β-halohydrins using active magnesium halides is described. The conversion proceeds smoothly at room temperature with high regioselectivity and good yields even when sensitive functional groups are present.

Key words

epoxide - β-halohydrin - cleavage - regioselectivity - chemoselectivity

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8

General Procedure
To the solution of epoxide (5 mmol) in CH2Cl2 (8 mL) was added active MgX2˙THF (2.0 equiv, M = 1.78 mol/L) at r.t. The reaction was stirred at the same temperature for 1 min and then quenched with sat. aq NH4Cl. The solvent was removed under vacuum. and the residue was extracted with EtOAc. The combined organic layer was washed with H2O and brine, dried over anhyd Na2SO4, and concentrated under reduced pressure. Purification of the residue was by chromatography on SiO2 to give the product.

9

Spectral Data of Compounds 1a-c, 2a,b, 3c, 7a, 7a′, 7b, 7b′ matched in all respects with reported data.
Analytical Data of Compounds 3-6
Compound 3a: ¹H NMR (400 MHz, CDCl3): δ = 3.78 (m, 1 H), 3.53 (dd, J = 12.0, 4.0 Hz, 1 H), 3.43-3.36 (m, 3 H), 2.39 (br, 1 H), 1.92-1.82 (m, 2 H), 1.62-1.51 (m, 4 H). ¹³C NMR (100 MHz, CDCl3): δ = 70.8, 40.3, 34.1, 33.6, 32.4, 24.3. IR (neat): 3393, 2941, 2864, 1432, 1259, 1050, 666, 561 cm-¹. HRMS (EI): m/z [M - H]+ calcd for C6H12Br2O: 258.9234; found: 258.9156.
Compound 3b: ¹H NMR (400 MHz, CDCl3): δ = 3.56-3.48 (m, 1 H), 3.42-3.35 (m, 3 H), 3.22 (t, J = 8.0 Hz, 1 H), 2.34 (br, 1 H), 1.90-1.84 (m, 2 H), 1.60-1.48 (m, 4 H). ¹³C NMR (100 MHz, CDCl3): δ = 70.7, 35.6, 33.7, 32.4, 24.3, 16.4.
Compound 4a: ¹H NMR (400 MHz, CDCl3): δ = 4.74 (dd, J = 28.0, 8.0 Hz, 2 H), 3.98-3.92 (m, 1 H), 3.75 (dd, J = 12.0, 4.0 Hz, 1 H), 3.67 (dd, J = 12.0, 4.0 Hz, 1 H), 3.57 (dd, J = 12.0, 8.0 Hz, 1 H), 3.41 (s, 3 H), 2.75 (br, 1 H), 2.63 (d, J = 4.0 Hz, 2 H), 0.14 (s, 9 H). ¹³C NMR (100 MHz, CDCl3): δ = 102.6, 96.6, 87.4, 76.7, 72.0, 56.0, 36.4, 22.4, -0.0(4). IR (neat): 3437, 2958, 2899, 2177, 1420, 1250, 699, 646 cm-¹. HRMS (EI): m/z [M - H]+ calcd for C11H21BrO3Si: 307.0443; found: 307.0349.
Compound 4b: ¹H NMR (400 MHz, CDCl3): δ = 4.77-4.68 (m, 2 H), 3.75-3.66 (m, 2 H), 3.49-3.45 (m, 1 H), 3.40 (d, J = 8.0 Hz, 3 H), 3.35-3.31 (m, 1 H), 2.75 (br, 1 H), 2.61 (d, J = 8.0 Hz, 2 H), 0.12 (d, J = 8.0 Hz, 9 H). ¹³C NMR (100 MHz, CDCl3): δ = 102.6, 96.7, 87.4, 78.4, 72.2, 56.1, 22.4, 11.0, -0.0(0).
Compound 5a: ¹H NMR (400 MHz, CDCl3): δ = 3.79-3.72 (m, 2 H), 3.59 (dd, J = 12.0, 4.0 Hz, 1 H), 3.51-3.43 (m, 2 H), 3.35 (dd, J = 12.0, 8.0 Hz, 1 H), 2.76 (br, 2 H), 1.55-1.43 (m, 6 H), 1.40-1.30 (m, 4 H). ¹³C NMR (100 MHz, CDCl3): δ = 71.3, 71.0, 50.4, 40.4, 34.9, 34.0, 29.3, 29.2, 25.4, 25.3.
Compound 5b: ¹H NMR (400 MHz, CDCl3): δ = 3.78-3.73 (m, 1 H), 3.57 (dd, J = 8.0, 4.0 Hz, 1 H), 3.50-3.42 (m, 2 H), 3.32 (dd, J = 8.0, 4.0 Hz, 1 H), 3.21-3.17 (m, 1 H), 3.04 (br, 2 H), 1.55-1.39 (m, 6 H), 1.38-1.26 (m, 4 H). ¹³C NMR (100 MHz, CDCl3): δ = 71.3, 70.8, 50.3, 36.4, 34.0, 29.2, 25.5, 25.4, 16.3.
Compound 6a: ¹H NMR (400 MHz, CDCl3): δ = 3.85-3.79 (m, 2 H), 3.56 (dd, J = 12.0, 4.0 Hz, 1 H), 3.48-3.38 (m, 3 H), 2.14 (d, J = 4.0 Hz, 1 H), 1.61-1.50 (m, 4 H), 1.43-1.32 (m, 6 H), 0.91 (s, 9 H), 0.10 (d, J = 8.0 Hz, 6 H). ¹³C NMR (100 MHz, CDCl3): δ = 72.4, 71.0, 48.5, 40.6, 35.0, 34.8, 29.5, 25.8, 25.5, 24.7, 18.1, -4.5, -4.6. IR (neat): 3393, 2931, 2857, 1463, 1255, 1099, 837, 777 cm-¹.
Compound 6b: ¹H NMR (400 MHz, CDCl3): δ = 3.85-3.80 (m, 1 H), 3.56-3.48 (m, 1 H), 3.46-3.38 (m, 3 H), 3.25 (dd, J = 12.0, 8.0 Hz, 1 H), 2.03 (d, J = 8.0 Hz, 1 H), 1.66-1.53 (m, 4 H), 1.46-1.31 (m, 6 H), 0.91 (s, 9 H), 0.10 (d, J = 4.0 Hz, 6 H). ¹³C NMR (100 MHz, CDCl3): δ = 72.4, 70.9, 48.5, 36.5, 34.8, 29.5, 25.8, 25.6, 24.7, 18.1, 16.6, -4.4, -4.6.