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Synlett 2006(14): 2251-2255  
DOI: 10.1055/s-2006-948206
LETTER
© Georg Thieme Verlag Stuttgart · New York

Regioselective, Haloacylating Cleavage of an Oxirane System Mediated by Trifluoroacetic Anhydride/Trimethylsilyl Halides: An Efficient Entry to 2-Acyl-3-haloglycerols

Stephan D. Stamatov*a, Jacek Stawinski*b,c
a Department of Chemical Technology, University of Plovdiv, 24 Tsar Assen St., Plovdiv 4000, Bulgaria
b Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 106 91 Stockholm, Sweden
e-Mail: js@organ.su.se;
c Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland
Further Information

Publication History

Received 7 June 2006
Publication Date:
24 August 2006 (online)

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Abstract

Glycidyl esters in the presence of trifluoroacetic anhydride (TFAA) and trimethylsilyl halides (TMSX), undergo a regio­selective opening of the oxirane system with a subsequent migration of the acyl group to afford 1-trifluoroacetyl-2-acyl-3-haloglycerols. From these, the corresponding 2-acyl-3-haloglycerols can be obtained quantitatively and in high purity (>99%) without chromatographic purification.

Key words

glycidyl esters - trimethylsilyl halides - trifluoroacetic anhydride - 2-O-acylated 1,3-terminal halohydrins - 2-acylglycerol isosters

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General Procedure for the Synthesis of 1-Trifluoro-acetyl-2-acyl-3-haloglycerols 3-6 (Step A). (S)-(+)-2-(Oleoyloxymethyl)oxirane (1) {[α]D 20 +13.89 (c 5.66, CHCl3)} and (rac)-(±)-2-(2,4,6-trimethylbenzoyloxy-methyl)oxirane (2) were obtained by direct acylation of chiral or racemic glycidols as described elsewhere. [32] The R f values refer to mobility on a silica gel plates using the solvent system: pentane-toluene-EtOAc = 40:50:10 (v/v/v).
To a solution of the starting substrate 1, 2 (1.00 mmol) in CH2Cl2 (3.0 mL), a mixture of TFAA (4.00-5.00 mmol) and trimethylsilyl halide (1.20-4.00 mmol), prepared in the same solvent (3.0 mL), was added at -20 °C and the reaction system was kept under argon at r.t. for 2-5 h. Then, CH2Cl2 and volatile reaction components were evaporated in vacuo, the residue was taken in toluene (5.0 mL) and passed through a silica gel pad (ca. 5 g) prepared in the same solvent. The support was washed with toluene (ca. 100 mL), fractions containing the target compound were combined, the eluent was removed under reduced pressure, and the rest was kept under high vacuum at r.t. for 2-3 h to afford the rearranged 2-O-acylated halohydrin 3-6 (purity >99%, 1H NMR spectroscopy).
1-Trifluoroacetyl-2-oleoyl-3-chloro-rac-glycerol (3): obtained from 1 (0.338 g, 1.00 mmol), TFAA (0.556 mL, 4.00 mmol) and TMSCl (0.505 mL, 4.00 mmol) for 5 h. Yield: 0.428 g (91%, colorless oil); R f = 0.68. Anal. Calcd (%) for C23H38ClF3O4 (470.99): C, 58.65; H, 8.13; Cl, 7.53. Found: C, 58.72; H, 8.10; Cl, 7.51.
1-Trifluoroacetyl-2-oleoyl-3-bromo-rac-glycerol (4): obtained from 1 (0.338 g, 1.00 mmol), TFAA (0.556 mL, 4.00 mmol) and TMSBr (0.259 mL, 2.00 mmol) for 3 h. Yield: 0.479 g (93%, colorless oil); R f = 0.67. Anal. Calcd (%) for C23H38BrF3O4 (515.44): C, 53.59; H, 7.43; Br, 15.50. Found: C, 53.56; H, 7.41; Br, 15.51.
1-Trifluoroacetyl-2-oleoyl-3-iodo-rac-glycerol (5): obtained from 1 (0.338 g, 1.00 mmol), TFAA (0.695 mL, 5.00 mmol) and TMSI (0.163 mL, 1.20 mmol) for 2 h. Yield: 0.534 g (95%, colorless oil); R f = 0.66. Anal. Calcd (%) for C23H38F3IO4 (562.44): C, 49.11; H, 6.81; I, 22.56. Found: C, 49.18; H, 6.78; I, 22.51.
1-Trifluoroacetyl-2-(2,4,6-trimethylbenzoyl)-3-bromo-rac-glycerol (6): obtained from 2 (0.220 g, 1.00 mmol), TFAA (0.556 mL, 4.00 mmol) and TMSBr (0.259 mL, 2.00 mmol) for 3 h. Yield: 0.353 g (89%, colorless oil); R f = 0.71. Anal. Calcd (%) for C15H16BrF3O4 (397.18): C, 45.36; H, 4.06; Br, 20.12. Found: C, 45.41; H, 4.01; Br, 20.18.

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General Procedure for the Synthesis of 2-Acyl-3-haloglycerols 7-10 (Step B).
To a solution of trifluoroacetyl halohydrin 3-6 (1.00 mmol) in pentane-CH2Cl2 (3:1, v/v, 5.0 mL), a mixture of pyridine (0.8 mL, 10 mmol) and MeOH (10.1 mL, 250 mmol) in the same solvents (5.0 mL) was added at 0 °C and the reaction system was left at r.t. for 20 min. Solvents were evaporated under reduced pressure (bath temp. 50 °C) and the residue was kept under high vacuum at r.t. for 2-3 h to give the deprotected haloalkanol 7-10 (purity >99%, 1H NMR spectroscopy).
2-Oleoyl-3-chloro-rac-glycerol (7): obtained from 3 (0.471 g, 1.00 mmol). Yield: 0.374 g (100%, colorless oil); R f = 0.25. Anal. Calcd (%) for C21H39ClO3 (374.98): C, 67.26; H, 10.48; Cl, 9.45. Found: C, 67.22; H, 10.51; Cl, 9.50.
2-Oleoyl-3-bromo-rac-glycerol (8): obtained from 4 (0.515 g, 1.00 mmol). Yield: 0.419 g (100%, colorless oil); R f = 0.23. Anal. Calcd (%) for C21H39BrO3 (419.44): C, 60.13; H, 9.37; Br, 19.05. Found: C, 60.08; H, 9.40; Br, 19.00.
2-Oleoyl-3-iodo-rac-glycerol (9): obtained from 5 (0.562 g, 1.00 mmol). Yield: 0.466 g (100%, yellowish oil); R f = 0.34. Anal. Calcd (%) for C21H39IO3 (466.44): C, 54.07; H, 8.43; I, 27.21. Found: C, 54.13; H, 8.40; I, 27.24.
2-(2,4,6-Trimethylbenzoyl)-3-bromo-rac-glycerol (10): obtained from 6 (0.397 g, 1.00 mmol). Yield: 0.300 g (100%, colorless oil); R f = 0.24. Anal. Calcd (%) for C13H17BrO3 (301.18): C, 51.84; H, 5.69; Br, 26.53. Found: C, 51.79; H, 5.72; Br, 26.57.