Download PDF
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;
Further Information

Publication History

Received 18 December 2008
Publication Date:
13 May 2009 (online)

    Permissions and Reprints All articles of this category

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

    References and Notes

  • 1a Piva O. Tetrahedron Lett.  1992,  33:  2459 
    Google Scholar
  • 1b Berkessel A. Rollmann C. Chamouleau F. Labs S. May O. Gröger H. Adv. Synth. Catal.  2007,  349:  2697 
    Google Scholar
  • 1c de Jong RM. Tiesinga JJW. Villa A. Tang L. Janssen DB. Dijkstra BW. J. Am.Chem. Soc.  2005,  127:  13338 
    Google Scholar
  • For reviews, see:
  • 2a Moore RE. In Marine Natural Products   Vol. 1:  Scheuer PJ. Academic; New York: 1978.  Chap. 2.
    Google Scholar
  • 2b Fenical W. In Marine Natural Products   Vol. 2:  Scheuer PJ. Academic; New York: 1980.  p.174 
    Google Scholar
  • 2c Barrow KD. In Marine Natural Products   Vol. 5:  Scheuer PJ. Academic; New York: 1983.  p.51 
    Google Scholar
  • 3a Righi G. Franchini T. Bonini C. Tetrahedron Lett.  1998,  39:  2385 
    Google Scholar
  • 3b Babudri F. Fiandanese V. Marchese G. Punzi A. Tetrahedron  2001,  57:  549 
    Google Scholar
  • 3c Boukhris S. Souizi A. Tetrahedron Lett.  2003,  44:  3259 
    Google Scholar
  • 4a Sharghi H. Eskandari MM. Tetrahedron  2003,  59:  8509 
    Google Scholar
  • 4b Konnaklieva ML. Dahi ML. Turos E. Tetrahedron Lett.  1992,  33:  7093 
    Google Scholar
  • 4c Stewart CA. Vander Werf CA. J. Am. Chem. Soc.  1954,  76:  1259 
    Google Scholar
  • 4d Kotsuki H. Shimanouchi T. Tetrahedron Lett.  1996,  37:  1845 
    Google Scholar
  • 4e Sabitha G. Babu RS. Rajkumar M. Reddy CS. Yadav JS. Tetrahedron Lett.  2001,  42:  3955 
    Google Scholar
  • 4f Pinto RMA. Salvador JAR. Roux CL. Tetrahedron  2007,  63:  9221 
    Google Scholar
  • 4g Das B. Krishnaiah M. Venkateswarlu K. Tetrahedron Lett.  2006,  47:  4457 
    Google Scholar
  • 5a Wu J. Sun X. Sun W. Ye S. Synlett  2006,  2489 
    Google Scholar
  • 5b Niknam K. Nasehi T. Tetrahedron  2002,  58:  10259 
    Google Scholar
  • 6 Bajwa JS. Anderson RC. Tetrahedron Lett.  1991,  32:  3021 
    CrossrefGoogle Scholar
  • 7a Ranu BC. Banerjee S. J. Org. Chem.  2005,  70:  4517 
    Google Scholar
  • 7b Ranu BC. Adak L. Banerjee S. Can. J. Chem.  2007,  85:  366 
    Google Scholar
  • 10 Eisch JJ. Liu ZR. Zheng GX. J. Org. Chem.  1992,  57:  5140 
    CrossrefGoogle Scholar
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.