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

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.

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

References and Notes

1a Sugiura T. Kondo S. Sukagawa A. Nakane S. Shinoda A. Itoh K. Yamashita A. Waku K. Biochem. Biophys. Res. Commun.  1995,  215:  89 

1b Sugiura T. Kondo S. Kishimoto S. Miyashita T. Nakane S. Kodaka T. Suhara Y. Takayama H. Waku K. J. Biol. Chem.  2000,  275:  605 

1c Sugiura T. Waku K. Chem. Phys. Lipids  2000,  108:  89 

1d Sugiura T. Yoshinaga N. Waku K. Neurosci. Lett.  2001,  297:  175 

1e Di Marzo V. Melck D. De Petrocellis L. Bisogno T. Prostag. Other Lipid Mediat.  2000,  61:  43 

2 Small DM. Ann. Rev. Nutr.  1991,  11:  413 

3 Iwasaki Y. Yamane T. J. Mol. Catal. B: Enzym.  2000,  10:  129 

4a Mergen F. Lambert DM. Saraiva JCG. Poupaert JH. Dumont P. J. Pharm. Pharmacol.  1991,  43:  815 

4b Deverre JR. Loiseau P. Puisieux F. Gayral P. Letourneux Y. Couvreur P. Benoit JP. Arzneim.-Forsch./Drug Res.  1992,  42:  1153 

4c Lambert DM. Neuvens L. Mergen F. Gallez B. Poupaert JH. Ghyselburton J. Maloteaux JM. Dumont P. J. Pharm. Pharmacol.  1993,  45:  186 

4d Garzon-Aburbeh A. Poupaert JH. Claesen M. Dumont P. Atassi G. J. Med. Chem.  1983,  26:  1200 

4e Paris GY. Garmaise DL. Cimon DG. Swett L. Carter GW. Young P. J. Med. Chem.  1979,  22:  683 

5 Suhara Y. Takayama H. Nakane S. Miyashita T. Waku K. Sugiura T. Chem. Pharm. Bull.  2000,  48:  903 

6 Suhara Y. Nakane S. Arai S. Takayama H. Waku K. Ishima Y. Sugiura T. Bioorg. Med. Chem. Lett.  2001,  11:  1985 

7 Razdan RK. Mahadevan A. Chem. Phys. Lipids  2002,  121:  21 

8 Houte H. Partali V. Sliwka H.-R. Quartey EGK. Chem. Phys. Lipids  2000,  105:  105 

9 Innis SM. Dyer R. Nelson CM. Lipids  1994,  29:  541 

10 Prades J. Funari SS. Escriba PV. Barcelo F. J. Lipid Res.  2003,  44:  1720 

11 Burchardt A. Takahashi T. Takeuchi Y. Haufe G. J. Org. Chem.  2001,  66:  2078 

12 Strawn LM. Martell RE. Simpson RU. Leach KL. Counsell RE. J. Med. Chem.  1989,  32:  2104 

13 Weichert JP. Longino MA. Bakan DA. Spigarelli MG. Chou T. Schwendner SW. Counsell RE. J. Med. Chem.  1995,  38:  636 

14a Han LN. Razdan RK. Tetrahedron Lett.  1999,  40:  1631 

14b Cartoni A. Margonelli A. Angelini G. Finazzi-Agro A. Maccarrone M. Tetrahedron Lett.  2004,  45:  2723 

14c Seltzman HH. Fleming DN. Hawkins GD. Carroll FI. Tetrahedron Lett.  2000,  41:  3589 

15 Schmid PC. Schwartz KD. Smith CN. Krebsbach RJ. Berdyshev EV. Schmid HHO. Chem. Phys. Lipids  2000,  104:  185 

16 Rouzer CA. Ghebreselasie K. Marnett LJ. Chem. Phys. Lipids  2002,  119:  69 

17a Martin JB. J. Am. Chem. Soc.  1953,  75:  5483 

17b Serdarevich B. J. Am. Oil Chem. Soc.  1967,  44:  381 

17c Mattson FH. Volpenhein RA. J. Lipid Res.  1962,  3:  281 

17d Kodali DR. Tercyak A. Fahey DA. Small DM. Chem. Phys. Lipids  1990,  52:  163 

18a Martin JD. Palazon JM. Perez C. Ravelo JL. Pure Appl. Chem.  1986,  58:  395 

18b Martin JD. Perez C. Ravelo JL. J. Am. Chem. Soc.  1986,  108:  7801 

18c vanDeenen LM. deHaas GH. Biochim. Biophys. Acta  1963,  70:  538 

19 Righi G. Bonini C. Recent Res. Dev. Org. Chem.  1999,  3:  343 

20 Brachwitz H. Langen P. Dube G. Schildt J. Paltauf F. Hermetter A. Chem. Phys. Lipids  1990,  54:  89 

21a Bonini C. Righi G. Synthesis  1994,  225 

21b Azzena F. Calvani F. Crotti P. Gardelli C. Macchia F. Pineschi M. Tetrahedron  1995,  51:  10601 

21c Bajwa JS. Anderson RC. Tetrahedron Lett.  1991,  32:  3021 

21d Righi G. Pescatore G. Bonadies F. Bonini C. Tetrahedron  2001,  57:  5649 

21e Kotsuki H. Shimanouchi T. Ohshima R. Fujiwara S. Tetrahedron  1998,  54:  2709 

21f Bartas-Yacoubou J.-M. Maduike N. Kyere S. Doan L. Whalen DL. Tetrahedron Lett.  2002,  43:  3781 

22a Onaka M. Sugita K. Takeuchi H. Izumi Y. J. Chem. Soc., Chem. Commun.  1988,  1173 

22b Chini M. Crotti P. Gardelli C. Macchia F. Tetrahedron  1992,  48:  3805 

23a Gao L.-X. Murai A. Chem. Lett.  1989,  357 

23b Gao L.-X. Murai A. Chem. Lett.  1991,  1503 

24a Konaklieva MI. Dahl ML. Turos E. Tetrahedron Lett.  1992,  33:  7093 

24b Sharghi H. Eskandari MM. Tetrahedron  2003,  59:  8509 

24c Sharghi H. Eskandari MM. Ghavami R. J. Mol. Catal. A: Chem.  2004,  215:  55 

24d Sharghi H. Eskandari MM. Synthesis  2002,  1519 

24e Soroka M. Goldeman W. Malysa P. Stochaj M. Synthesis  2003,  2341 

25 Parfenov EA. Serebrennikova GA. Preobrazhenskii NA. Zh. Org. Khim.  1967,  3:  1951 

26a Sharpless KB. Teranishi AY. Backvall JE. J. Am. Chem. Soc.  1977,  99:  3120 

26b Backvall JE. Young MW. Sharpless KB. Tetrahedron Lett.  1977,  18:  3523 

27 Iqbal J. Amin Khan M. Srivastava RR. Tetrahedron Lett.  1988,  29:  4985 

28 Shibata I. Baba A. Matsuda H. Tetrahedron Lett.  1986,  27:  3021 

29 Iranpoor N. Zeynizadeh B. J. Chem. Res., Synop.  1998,  582 

30 Oriyama T. Ishiwata A. Hori Y. Yatabe T. Hasumi N. Koga G. Synlett  1995,  1004 

31 Stamatov SD. Stawinski J. Tetrahedron Lett.  2002,  43:  1759 

32 Stamatov SD. Stawinski J. Tetrahedron  2005,  61:  3659 

33 Stamatov SD. Stawinski J. Bioorg. Med. Chem. Lett.  2006,  16:  3388 

34 Stamatov SD. Stawinski J. Synlett  2005,  2587 

35 In separate experiments we found that reaction of 1 with TFAA and tetrabutylammonium halides or with TFAA and TMSBr in the presence of pyridine, occurred without acyl migration and involved a nucleophilic opening of the oxirane ring with halide ion, facilitated by electrophilic catalysis exerted by TFAA

36

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.

37

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.