A facile transfer fluorination approach to the synthesis of N-fluoro sulfonamides

Tetrahedron Letters

Volumn 41, Issue 18, 2000, Pages 3291-3294

  Taylor, Dawne M ^a   Meier, G Patrick ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Fluorine and compounds; Sulfonamide; Transfer reaction

Indexed keywords

BENZENESULFONAMIDE DERIVATIVE; N FLUOROBENZENESULFONIMIDE; SULFONAMIDE; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; FLUORINATION; REACTION ANALYSIS; STOICHIOMETRY;

EID: 0034728842     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(00)00525-6     Document Type: Article

References (23)

1. (a) Fluorine in Bioorganic Chemistry; Welch, J. T.; Eswarakrishnan, S., Eds.; John Wiley & Sons: New York, 1991.
2. (b) Biomedical Frontiers of Fluorine Chemistry; Ojima, I.; McCarthy, J. R.; Welch, J. T., Eds.; American Chemical Society: Washington, DC, 1996.
3. (c) Biomedicinal Aspects of Fluorine Chemistry; Filler, R.; Kobayashi, Y., Ed.; Kodanasha Ltd, Elsevier Biomedical Press: New York, 1982.
4. For opposing opinions on the ability of fluorine to act as a hydrogen bond acceptor, see: (a) Dunitz, J. D.; Taylor, R. Chem. Eur. J. 1997, 3, 989 and
5. For opposing opinions on the ability of fluorine to act as a hydrogen bond acceptor, see: (b) Howard, J. A. K.; Hoy, B. J.; O'Hagan, D.; Smith, G. T. Tetrahedron 1996, 52, 12613.
6. (a) Bondi, A. J. Phys. Chem. 1964, 68, 441.
7. (b) O'Hagan, D.; Rzepa, H. S. J. Chem. Soc., Chem. Commun. 1997, 645.
8. Carbon-Fluorine Compounds: Chemistry, Biochemistry and Biological Activities; Ciba Foundation Symposium, Associated Scientific Publishers: Amsterdam, 1972.
9. Barnette, W. E. J. Am. Chem. Soc. 1984, 106, 452.
10. For a recent review on fluorination, see: Lal, G. S.; Pez, G. P.; Syvert, R. G. Chem. Rev. 1996, 96, 1737.
11. 4, Aldrich); N-fluoro-2,4,6-trimethylpyridinium triflate (NFTPT, Aldrich); N-fluorobenzenesulfonimide (Accufluor, NFSi, Aldrich). A list of the commercial and non-commercial fluorinating agents, as of 1996, with their structures can be found in Ref. 6. We thank Dr. George Shia of AlliedSignal for the generous gift of NFSi.
12. To the best of our knowledge, this is the first report of a heteroatom-to-heteroatom transfer fluorination. For recent examples of other transfer (heteroatom-to-carbon) fluorinations, see: (a) Banks, E. R. E.; Besheesh, M. K.; Mohialdin-Khaffaf, S. N.; Sharif, I. J. Fluorine Chem. 1997, 81, 157.
13. To the best of our knowledge, this is the first report of a heteroatom-to-heteroatom transfer fluorination. For recent examples of other transfer (heteroatom-to-carbon) fluorinations, see: (b) Okaonya, J. F.; Johnson, M. C.; Hoffman, R. V. J. Org. Chem. 1998, 63, 6409.
14. To the best of our knowledge, this is the first report of a heteroatom-to-heteroatom transfer fluorination. For recent examples of other transfer (heteroatom-to-carbon) fluorinations, see: (c) Davis, A. F.; Zhou, P.; Murphy, C. K.; Sundarababu, G.; Qi, H.; Han, W.; Przeslawski, R. M.; Chen, B.-C.; Carroll, P. J. J. Org. Chem. 1998, 63, 2273.
15. To the best of our knowledge, this is the first report of a heteroatom-to-heteroatom transfer fluorination. For recent examples of other transfer (heteroatom-to-carbon) fluorinations, see: (d) Umemoto, T.; Nagayoshi, M.; Adachi, K.; Tomizawa, G. J. Org. Chem. 1998, 63, 3379.
16. To the best of our knowledge, this is the first report of a heteroatom-to-heteroatom transfer fluorination. For recent examples of other transfer (heteroatom-to-carbon) fluorinations, see: (e) Kotoris, C. C.; Chen, M.-J.; Taylor, S. D. J. Org. Chem. 1998, 63, 8052.
17. Christe, K. O. J. Fluorine Chem. 1984, 25, 269.
18. The sulfonamide was recovered in 83% yield in reactions when 1.2 equiv. of KH and 1.3 equiv. of NFSi were used. Quenching the fluorination reaction with methyl iodide under these conditions resulted in recovery of the N-H sulfonamide in a similar yield, indicating that there was no anion present at the end of the reaction. Direct reaction of the sulfonamide anion produced under these conditions with methyl iodide resulted in complete (>95%) conversion to the N-methyl sulfonamide, indicating that the experimental conditions gave complete deprotonation of the sulfonamide. The fluorinated sulfonamide was stable to the conditions of the reaction work-up (>90% recovery). The mechanism for formation of the recovered sulfonamide is not known.
19. (a) Differding, E.; Ofner, H. J. Synlett 1991, 187;
20. (b) Differding, D.; Duthaler, R. O.; Kreeiger, A.; Ruegg, G. M.; Schmit, C. Synlett 1991, 395.
21. Reaction of the less hindered N-ethyl and N-phenethyl sulfonamides in THF gave the N-phenyl, p-tolyl sulfonimides as the major side products (21% in both reactions). The identities of these imides were secured by direct synthesis. This product is proposed to be formed by nucleophilic attack of the sulfonamide anion on the sulfonyl group, rather than at the fluorine, of the N-fluoro benzenesulfonimide.
22. Over nine products were formed in this reaction. This reaction was considered to be a test of the hypothesis that the mechanism of this fluorination is a Single Electron Transfer process (Ref. 6, page 1750). However, the results obtained are not conclusive.
23. 2, 20% ethyl acetate/hexanes).