Synlett 2003(10): 1530-1532
DOI: 10.1055/s-2003-40865
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Synthesis of Fluorohydrines via SN2-Type Ring-Opening of Epoxides with TBABF-KHF2

Yuriko Akiyama, Tsuyoshi Fukuhara, Shoji Hara*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Fax: +81(11)7066556; e-Mail: hara@org-mc.eng.hokudai.ac.jp;
Further Information

Publication History

Received 4 June 2003
Publication Date:
24 July 2003 (online)

Abstract

We found that the ring-opening fluorination of terminal epoxides using TBABF-KHF2 proceeds with high selectivity through the SN2 mechanism. As TBABF-KHF2 is easily obtainable, is stable, and can be used in glassware, it can be a useful reagent for 1-fluoro-2-alkanol synthesis from the terminal epoxides.

    References

  • 1a Mascaretti OA. Aldrichimica Acta  1993,  26:  47 
  • 1b Bonini C. Righi G. Synthesis  1994,  225 ; and the references cited therein
  • 2 Umezawa J. Takahashi O. Furuhashi K. Nohira H. Tetrahedron: Asymmetry  1993,  4:  2053 
  • 3 Suga H. Hamatani T. Schlosser M. Tetrahedron  1990,  46:  4247 
  • 4 Seto H. Qian Z. Yoshioka H. Uchibori Y. Umeno M. Chem. Lett.  1991,  1185 
  • 5a Landini D. Maia A. Rampoldi A. J. Org. Chem.  1989,  54:  328 
  • 5b Christe KO. Wilson WW. Wilson RD. Bau R. Feng J. J. Am. Chem. Soc.  1990,  112:  7619 
  • 6 Albanese D. Landini D. Penso M. J. Org. Chem.  1998,  63:  9587 
  • TBABF was previously used for the halogen exchange fluorination reaction in polar solvents, see:
  • 7a Bosch P. Camps F. Chamorro E. Gasol V. Guerrero A. Tetrahedron Lett.  1987,  28:  4733 
  • 7b Moughamir K. Atmani A. Mestdagh H. Rolando C. Francesch C. Tetrahedron Lett.  1998,  39:  7305 
  • 9a Landini D. Penso M. Tetrahedron Lett.  1990,  31:  7209 
  • 9b Landini D. Albanese D. Penso M. Tetrahedron  1992,  48:  4163 
  • 10 Sattler A. Haufe G. J. Fluorine Chem.  1994,  69:  185 
  • 13 Matsuda T. Harada T. Nakajima N. Itoh T. Nakamura K. J. Org. Chem.  2000,  65:  157 
  • 14 Takano S. Yanase M. Ogasawara K. Chem. Lett.  1989,  1689 
  • 18 Camps F. Chamorro E. Casol V. Guerrero A. J. Org. Chem.  1989,  54:  4294 
  • 19 Sharma RK. Fry JL. J. Org. Chem.  1983,  48:  2112 
8

The generated TBAF must be converted to the stable TBABF again by KHF2 before the decomposition to Bu3N. [9] As KHF2 is slightly soluble in the reaction mixture, further addition of KHF2 was not effective.

11

Enantiomeric excess values of (S)-2b and (R)-3b were determined from 19F NMR after conversion to MTPA esters.

12

The representative procedure for 2a is as follows: To a 1 M THF solution of TBAF (30 mL, 30 mmol) in a glass vessel was added 46% aq HF (1.3 g, 30 mmol) and the volatile part was removed by evaporator to give a crude TBABF. The crude TBABF, containing a little water, is storable in a glass bottle. [15] The crude TBABF (845 mg, 3 mmol) and KHF2 (24 mg, 0.3 mmol) were put in a glass vessel and water was completely removed (for 15 min at 100 °C and 0.55 mmHg). After cooling to room temperature, heptane (0.1 mL) [16] and 1a (1 mmol) were added. The mixture was kept at 120 °C for 4 h and then cooled to room temperature again. To the reaction mixture, 2 mL of water was added and the mixture was extracted with ether (2 mL × 3). NMR yield and the product ratio were determined from 19F NMR using FCH2CH2OH as an internal standard. Isolation was carried out by column chromatography (silica gel/hexane-ether) after concentration. 2a: IR (film) 3390, 2930, 1460 cm-1; 1H NMR (400 MHz, CDCl3) δ 4.50-4.20 (m, 2 H), 3.89-3.86 (m, 1 H), 2.00 (s, 1 H), 1.48-1.43 (m, 3 H), 1.33-1.28 (m, 7 H), 0.89 (t, 3 H, J = 7.0 Hz); 19F NMR (376 MHz, CDCl3) δ -228.81 (dt, J = 18.3 Hz, 47.7 Hz, 1 F); 3a: IR (film) 3365, 2930, 1466 cm-1; 1H NMR (400 MHz, CDCl3) δ 4.58 (dm, J = 50.3 Hz, 1 H), 3.79-3.61 (m, 2 H), 1.88 (t, J = 6.3 Hz, 1 H), 1.75-1.30 (m, 12 H), 0.89 (t, 3 H, J = 6.8 Hz); 19F NMR (376 MHz, CDCl3) δ -190.03 to -190.42 (m, 1 F).

15

Complete removal of water gave pure TBABF as a highly viscous liquid, [17] which is difficult to handle. Therefore, it is better to store the crude TBABF and to remove the water completely just before use. [18] TBABF is commercially available and TBABF obtained from Tokyo Kasei Kogyo Co., Ltd. showed the same reactivity.

16

Heptane was used to wash the substrates attached on the wall of the vessel during the reaction, and in a larger-scale experiment, the solvent is not necessary.

17

Spectra data of TBABF thus prepared coincided with the reported ones; 19F NMR (CD2Cl2, -80 °C) δ -151.5 (d, J HF = 123.0 Hz), lit. [19] (CD2Cl2, -80 °C) δ -147.5 (d, J HF = 123.3 Hz).