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

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.

epoxide - β-halohydrin - cleavage - regioselectivity - chemoselectivity

References and Notes

1a Piva O. Tetrahedron Lett.  1992,  33:  2459 

1b Berkessel A. Rollmann C. Chamouleau F. Labs S. May O. Gröger H. Adv. Synth. Catal.  2007,  349:  2697 

1c de Jong RM. Tiesinga JJW. Villa A. Tang L. Janssen DB. Dijkstra BW. J. Am.Chem. Soc.  2005,  127:  13338 

For reviews, see:

2a Moore RE. In Marine Natural Products   Vol. 1:  Scheuer PJ. Academic; New York: 1978.  Chap. 2.

2b Fenical W. In Marine Natural Products   Vol. 2:  Scheuer PJ. Academic; New York: 1980.  p.174 

2c Barrow KD. In Marine Natural Products   Vol. 5:  Scheuer PJ. Academic; New York: 1983.  p.51 

3a Righi G. Franchini T. Bonini C. Tetrahedron Lett.  1998,  39:  2385 

3b Babudri F. Fiandanese V. Marchese G. Punzi A. Tetrahedron  2001,  57:  549 

3c Boukhris S. Souizi A. Tetrahedron Lett.  2003,  44:  3259 

4a Sharghi H. Eskandari MM. Tetrahedron  2003,  59:  8509 

4b Konnaklieva ML. Dahi ML. Turos E. Tetrahedron Lett.  1992,  33:  7093 

4c Stewart CA. Vander Werf CA. J. Am. Chem. Soc.  1954,  76:  1259 

4d Kotsuki H. Shimanouchi T. Tetrahedron Lett.  1996,  37:  1845 

4e Sabitha G. Babu RS. Rajkumar M. Reddy CS. Yadav JS. Tetrahedron Lett.  2001,  42:  3955 

4f Pinto RMA. Salvador JAR. Roux CL. Tetrahedron  2007,  63:  9221 

4g Das B. Krishnaiah M. Venkateswarlu K. Tetrahedron Lett.  2006,  47:  4457 

5a Wu J. Sun X. Sun W. Ye S. Synlett  2006,  2489 

5b Niknam K. Nasehi T. Tetrahedron  2002,  58:  10259 

6 Bajwa JS. Anderson RC. Tetrahedron Lett.  1991,  32:  3021 

7a Ranu BC. Banerjee S. J. Org. Chem.  2005,  70:  4517 

7b Ranu BC. Adak L. Banerjee S. Can. J. Chem.  2007,  85:  366 

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.

10 Eisch JJ. Liu ZR. Zheng GX. J. Org. Chem.  1992,  57:  5140