Download PDF
Synlett 2007(3): 0439-0442  
DOI: 10.1055/s-2007-968031
LETTER
© Georg Thieme Verlag Stuttgart · New York

Direct Trifluoroacetylation Across a Trimethylsilyloxy System as a Stereo­specific, Chemo- and Regioselective Approach to C3-Vicinal Halohydrins

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, 10691 Stockholm, Sweden
e-Mail: js@organ.su.se;
c Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61704 Poznan, Poland
Further Information

Publication History

Received 11 November 2006
Publication Date:
07 February 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

Trifluoroacetylation across the silyloxy system of 1-acyl-2-O-trimethylsilyl-3-haloglycerols with trifluoroacetic anhydride (TFAA) in the presence of a halide anion (e.g. Bu4NX; X = Cl, Br or I), followed by removal of the trifluoroacetyl transient protection, provides a new, efficient entry to configurationally pure C3-vicinal halohydrins.

Key words

trimethylsilyl ethers - trifluoroacetic anhydride - tetra-n-butylammonium halides - C3-vicinal halohydrins - 1-acyl-3-halo-sn-glycerols

26

Typical Procedure for the Conversion of the Silyl Ethers 1-4 into the Corresponding Trifluoroacetate Derivatives 5-8 (Step A)
To a solution of silyl ether 1-4 (1.00 mmol) and tetra-n-butylammonium halide (2.00 mmol) in alcohol-free CH3Cl (5.0 mL), TFAA (0.278 mL, 2.00 mmol) was added and the reaction system was kept under argon at r.t. for 4-5 h. CH3Cl and volatile reaction components were evaporated in vacuo, the residue was taken in toluene (5.0 mL) and passed through a pad of silica gel (ca. 5 g) prepared in the same solvent. The support was washed with toluene (ca. 100 mL), fractions containing the target compounds were combined, the eluent was removed under reduced pressure, and the residue was kept under high vacuum at r.t. for 2-3 h to afford trifluoro-acetate 5-8 in >90% yields (purity >99% by 1H NMR).
1-Oleoyl-2-trifluoroacetyl-3-chloro-sn-glycerol (5): obtained from 1 (0.447 g, 1.00 mmol) and Bu4NCl (0.556 g, 2.00 mmol) for 5 h. Yield 0.429 g (91%, colorless oil); R f = 0.66 (pentane-toluene-EtOAc, 40:50:10); [α]D 20 +0.28 (c 9.65, CHCl3). Anal. Calcd (%) for C23H38ClF3O4 (470.99): C, 58.65; H, 8.13; Cl, 7.53. Found: C, 58.61; H, 8.10; Cl, 7.53%.
1-Oleoyl-2-trifluoroacetyl-3-bromo-sn-glycerol (6): obtained from 2 (0.492 g, 1.00 mmol) and Bu4NBr (0.645 g, 2.00 mmol) for 4 h. Yield 0.490 g (95%, colorless oil); R f = 0.69 (pentane-toluene-EtOAc, 40:50:10); [α]D 20 +3.47 (c 8.05, CHCl3). Anal. Calcd (%) for C23H38BrF3O4 (515.44): C, 53.59; H, 7.43; Br, 15.50. Found: C, 53.62; H, 7.37; Br, 15.55.
1-Oleoyl-2-trifluoroacetyl-3-iodo-sn-glycerol (7): obtained from 3 (0.539 g, 1.00 mmol) and Bu4NI (0.739 g, 2.00 mmol) for 4 h. Yield 0.529 g (94%, colorless oil); R f = 0.70 (pentane-toluene-EtOAc, 40:50:10); [α]D 20 +6.40 (c 10.01, CHCl3). Anal. Calcd (%) for C23H38IF3O4 (562.44): C, 49.11; H, 6.81; I, 22.56%. Found: C, 49.10; H, 6.80; I, 22.59.
1-Benzoyl-2-trifluoroacetyl-3-bromo-rac-glycerol (8): obtained from 4 (0.331 g, 1.00 mmol) and Bu4NBr (0.645 g, 2.00 mmol) for 4 h. Yield 0.334 g (94%, colorless oil); R f = 0.59 (pentane-toluene-EtOAc, 40:50:10). Anal. Calcd (%) for C12H10BrF3O4 (355.10): C, 40.59; H, 2.84; Br, 22.50. Found: C, 40.57; H, 2.80; Br, 22.50.

27

Typical Procedure for the Conversion of Trifluoro-acetates 5-8 into the Corresponding Halohydrin Derivatives 9-12 (Step B) To a solution of trifluoroacetyl halohydrin 5-8 (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 afford the deprotected haloalkanols 9-12 practically quantitatively (purity >99% by 1H NMR).
1-Oleoyl-3-chloro-sn-glycerol (9): obtained from 5 (0.471 g, 1.00 mmol). Yield 0.375 g (100%, colorless oil); R f = 0.32 (pentane-toluene-EtOAc, 40:50:10); [α]D 20 +3.00 (c 5.66, CHCl3). Anal. Calcd (%) for C21H39ClO3 (374.98): C, 67.26; H, 10.48; Cl, 9.45. Found: C, 67.30; H, 10.42; Cl, 9.42.
1-Oleoyl-3-bromo-sn-glycerol (10): obtained from 6 (0.515 g, 1.00 mmol). Yield 0.418 g (100%, colorless oil); R f = 0.33 (pentane-toluene-EtOAc, 40:50:10); [α]D 20 +2.45 (c 8.53, CHCl3). Anal. Calcd (%) for C21H39BrO3 (419.44): C, 60.13; H, 9.37; Br, 19.05. Found: C, 60.13; H, 9.42; Br, 19.10.
1-Oleoyl-3-iodo-sn-glycerol (11): obtained from 7 (0.562 g, 1.00 mmol). Yield 0.466 g (100%, white solid); R f = 0.36 (pentane-toluene-EtOAc, 40:50:10); [α]D 20 +2.39 (c 8.37, CHCl3); mp 33.0-33.6 °C; lit. [3] [α]D 20 +1.9 (c 10, CHCl3); mp 33.4 °C. Anal. Calcd (%) for C21H39IO3 (466.44): C, 54.07; H, 8.43; I, 27.21. Found: C, 54.15; H, 8.40; I, 27.27.
1-Benzoyl-3-bromo-rac-glycerol (12): obtained from 8 (0.355 g, 1.00 mmol). Yield 0.259 g (100%, colorless oil); R f = 0.32 (pentane-toluene-EtOAc, 40:50:10). Anal. Calcd (%) for C10H11BrO3 (259.10): C, 46.36; H, 4.28; Br, 30.84. Found: C, 46.42; H, 4.24; Br, 30.80.