Potassium Fluoride1

KF

[7789-23-3]  · FK  · Potassium Fluoride  · (MW 58.10)

(fluorinating reagent;1 desilylating reagent;11 base29)

Physical Data: mp 846 °C; bp 1505 °C; d 2.48 g cm-3; vapor pressure 1 mmHg at 885 °C.

Solubility: sol water, HF, NH3; slightly sol alcohol; insol most organic solvents.

Form Supplied in: white to colorless crystals and powder.

Handling, Storage, and Precautions: anhydrous KF should be handled and used under dry N2 for best results. KF reacts with acid to form the toxic gas hydrogen fluoride.

Fluorination Reagent.

Potassium fluoride is widely used as a fluorinating reagent to prepare various organic fluorides. Aromatic1 or vinyl fluorides2 activated by electron-withdrawing groups are readily prepared from an exchange reaction of KF with aromatic or vinyl chlorides in polar aprotic solvents such as DMF, DMSO, or tetramethylene sulfone. In the presence of Ph4PBr3 or phthaloyl difluoride,4 the fluoride ion replaces not only chlorine but also the nitro group in activated nitrobenzenes in DMSO. Reaction of polychlorobenzenes with KF gives mono-, di-, and trifluorobenzenes, depending on the reaction conditions.1f,5 Perfluorobenzene and perfluoropyridine have been available from chlorine-fluorine exchange reactions.6 The best results are obtained from heating a mixture of perchloroaromatic substrates and KF in the absence of solvent at an elevated temperature. Displacement of halide by fluoride ion also occurs with alkyl halides,7 particularly in the presence of CaF2,8 but it becomes more difficult with polychloroalkanes.

The chlorine-fluorine exchange reaction has been applied to prepare acyl or sulfonyl fluorides.9 Aryl acyl fluorides, alkyl acyl fluorides and sulfonyl fluorides are readily obtained from the reaction of acyl or sulfonyl chlorides with KF in the presence of CaF2 in MeCN at rt, although the reaction is slow with KF alone.8 Perfluorinated analogs are more active and the exchange reaction with KF is completed within a few hours in MeCN at rt.10

Desilylating Reagent.

Due to formation of a strong silicon-fluorine bond, KF readily reacts with trialkylsilyl ethers11 or acyl,12 alkyl,13 vinyl,14 and alkynyl15 silanes to remove the trialkylsilyl group. In the presence of a leaving group in the b-position, the silanes undergo smooth b-elimination reactions with KF in DMSO. Alkenes are obtained from saturated silanes (eq 1),16 and alkynes17 and allenes (eq 2)18 are produced from vinyl silanes. Silylvinyl triflates are decomposed with KF and a crown ether at -20 °C to give vinylidene carbenes in essentially quantitative yield and which can be trapped by alkenes to give cyclopropanes (eq 3).19

Vinyl trialkylsilyl ethers liberate ketones or aldehydes with KF and a proton source.20 In the presence of a carbonyl group, aldol condensation occurs to give b-hydroxy ketones (eq 4).21 The intramolecular aldol reaction also goes smoothly to produce a cyclic product (eq 5).22

In the presence of KF, perfluoroalkyl-23 or perfluorophenyltrimethylsilanes24 react with aldehydes, ketones, and acyl fluorides to give fluoro alcohols (eq 6). Sulfones were obtained in good yields when sulfonyl fluorides were used as substrates. These reactions usually proceed in aprotic solvents, such as MeCN and PhCN, at or near rt.

Certain carbon-silicon bonds can be oxidized with 30% Hydrogen Peroxide and KF to give the corresponding alcohols in good yields.25 This method is applicable to one-pot synthesis of anti-Markovnikov alcohols from terminal alkenes by hydrosilylation and oxidation (eq 7).26 The oxidizing ability of 90% H2O2 is only slightly greater than that of 30% H2O2; 70% t-Butyl Hydroperoxide is less active. Although m-Chloroperbenzoic Acid also works well, 30% H2O2 is more economical and the reaction is cleaner. The stereochemistry of the reaction center is retained under these conditions (eq 8).27 Various chiral diols are available by asymmetric catalytic intramolecular hydrosilylation of internally substituted alkenes using Rh complexes as catalysts, followed by oxidation with H2O2 and KF (eq 9).28 Vinylsilanes are also oxidized with H2O2 and KF to give ketones.26

KF promotes carbonylative coupling reactions of organofluorosilanes with aryl iodides in the presence of a palladium catalyst (eq 10).52

Use as a Base.29

KF in DMSO is a good dehydrohalogenation reagent for vinyl and alkyl halides to form alkynes,30 allenes,30 alkenes,31 and dienes.32 The presence of crown ethers facilitates the elimination reaction, particularly when MeCN is used as a solvent.30

Alkylation of alcohols,33 phenols,34 thiols,35 and amines36 with alkyl halides is promoted by KF. This method has been applied to synthesis of crown ethers.37 Heterocycles are also readily alkylated with allyl halides (eq 11).38 Arylation of phenols with activated aryl fluorides has been accomplished by using KF as a catalyst.39

The conversion of carboxylic acids and alkyl halides to esters (eq 12) has proven especially useful since employment of KF gives high yields of products.39 This reaction may be conducted by using the reactant acid as the bulk solvent; DMF can be used as a solvent when starting acids are solids.40 The alkyl iodides are the most reactive substrates.35

KF is widely used as a catalyst in Michael additions and aldol and Knoevenagel condensations. The use of KF has several advantages: a strong base is not required; catalytic amounts of KF are sufficient; separation of the catalyst is easy; yields are high with high selectivity; and the reactions are often successful when other strong bases are ineffective. Nitro compounds,41 nitriles,42 esters,43 1,3-diketones,44 and heterocycles such as imidazoles (eq 13)45 are usually used as Michael addition donors, and a,b-unsaturated aliphatic ketones, esters, nitro compounds, and nitriles are employed as the acceptors. Protic solvents such as ethanol are the most common, presumably due to the good solubility of KF in these solvents.46 MeCN and benzene are also employed, but the presence of a crown ether such as 18-Crown-6 is necessary for this reaction.47

Various nitro alcohols are obtained by aldol condensation of nitroalkanes with aldehydes.48 At elevated temperatures, the Knoevenagel reaction occurs to give unsaturated products (eq 14).49 The cyclization of 1,4-diketones to cyclopentenones is also achieved with KF and a crown ether in refluxing xylene (eq 15).50 Aromatic compounds are, however, usually obtained upon treatment of 1,3-diketones with KF in DMF (eq 16).51 Reaction of 1,2-diketones with KF/DMF gives 1,4-benzoquinone derivatives (eq 17).51

Related Reagents.

Lithium Fluoride; Potassium Fluoride-Alumina; Potassium Fluoride-Celite.


1. (a) Hudlicky, M. Chemistry of Organic Fluorine Compounds, 2nd ed.; Horwood: New York, 1992; pp 119-127. (b) Finger, G. C.; Kruse, C. W. JACS 1956, 78, 6034. (c) Starr, L. D.; Finger, G. C. CI(L) 1962, 1328. (d) Finger, G. C.; Dickerson, D. R.; Adl, T.; Hodgins, T. CC 1965, 430. (e) Ishikawa, N.; Kitazume, T.; Yamazaki, T.; Mochida, Y.; Tatsuno, T. CL 1981, 761. (f) Pews, R. G.; Gall, J. A. JFC 1990, 50, 371. (g) Suzuki, H.; Kimura, Y. JFC 1991, 52, 341. (h) Kimura, Y.; Suzuki, H. TL 1989, 30, 1271. (i)Reagent Chemicals: American Chemical Society Specifications, 8th ed.; ACS: Washington, 1993; pp 563-565.
2. (a) See Ref. 1(a), pp 117-118. (b) Wallenfels, K.; Witzler, F. T 1967, 23, 1359. (c) Bertram, H.-J.; Böhm, S.; Born, L. S 1991, 937.
3. (a) Clark, J. H.; Boechat, N. CI(L) 1991, 436. (b) Beaumont, A. J.; Clark, J. H. JFC 1991, 52, 295.
4. Maggini, M.; Passudetti, M.; Gonzales-Trueba, G.; Prato, M.; Quintily, U.; Scorrano, G. JOC 1991, 56, 6406.
5. (a) Pews, R. G.; Gall, J. A. JFC 1991, 52, 307. (b) Porwisiak, J.; Dmowski, W. JFC 1991, 51, 131.
6. (a) Fielding, H. C.; Gallimore, L. P.; Roberts, H. L.; Tittle, B. JCS(C) 1966, 2142. (b) Chambers, R. D.; Hutchinson, J.; Musgrave, W. K. R. JCS 1964, 3573.
7. See Ref. 1(a), pp 114-117. (b) Shahak, I.; Bergmann, E. D. JCS 1967, 319. (c) Stadlbauer, W.; Laschober, R.; Lutschouning, H.; Schindler, G.; Kappe, T. M 1992, 123, 617.
8. (a) Clark, J. H.; Hyde, A. J.; Smith, D. K. CC 1986, 791. (b) Ichihara, J.; Matsuo, T.; Hanafusa, T.; Ando, T. CC 1986, 793.
9. (a) Nesmejanov, A. N.; Kahn, E. J. CB 1934, 67, 370. (b) Davis, W.; Dick, J. H. JCS 1931, 2104. (c) Dear, R. E. A.; Gilbert, E. E. JOC 1968, 33, 1690.
10. Hu, L. Q.; DesMarteau, D. D. IC 1993, 32, 5007.
11. (a) Carpino, L. A.; Sau, A. C. CC 1979, 514. (b) Sinhababu, A. K.; Kawase, M.; Borchardt, R. T. S 1988, 710. (c) Rosini, G.; Marotta, E.; Righi, P.; Seerden, J. P. JOC 1991, 56, 6258.
12. (a) Degl'Innocenti, A.; Pike, S.; Walton, D. R. M.; Seconi, G.; Ricci, A.; Fiorenza, M. CC 1980, 1201. (b) Schinzer, D.; Heathcock, C. H. TL 1981, 22, 1881.
13. Alcaraz, C.; Carretero, J. C.; Dominguez, E. TL 1991, 32, 1385.
14. Chan, T. H.; Mychajlowskij, W. TL 1974, 3479.
15. (a) Semmelhack, M. F.; Neu, T.; Foubelo, F. TL 1992, 33, 3277. (b) Xu, Z.; Byun, H. S.; Bittman, R. JOC 1991, 56, 7183. (c) Courtemanche, G.; Normant, J. F. TL 1991, 32, 5317.
16. Miller, R. B.; Reichenbach, T. TL 1974, 543.
17. Cunico, R. F.; Dexheimer, E. M. JACS 1972, 94, 2868.
18. Chan, T. H.; Mychajlowskij, W.; Ong, B. S.; Harpp, D. N. JOC 1978, 43, 1526.
19. Stang, P. J.; Fox, D. P. JOC 1977, 42, 1667.
20. Chuit, C.; Foulon, J. P.; Normant, J. F. T 1981, 37, 1385.
21. Noyori, R.; Yokoyama, K.; Sakata, J.; Kuwajima, I.; Nakamura, E.; Shimizu, M. JACS 1977, 99, 1265.
22. Sano, T.; Toda, J.; Tsuda, Y. CPB 1992, 40, 36.
23. (a) Kotun, S. P.; Anderson, J. D. O.; DesMarteau, D. D. JOC 1992, 57, 1124. (b) Anderson, J. D. O.; Pennington, W. T.; DesMarteau, D. D. IC 1993, 32, 5079.
24. Patel, N. R.; Kirchmeier, R. L. IC 1992, 31, 2537.
25. (a) Tamao, K.; Ishida, N. JOM 1984, 269, C37. (b) Xi, Z.; Agback, P.; Plavec, J.; Sandström, A.; Chattopadhyaya, J. T 1992, 48, 349. (c) Tamao, K.; Kawachi, A.; Ito, Y. JACS 1992, 114, 3989. (d) Barrett, A. G. M.; Malecha, J. W. JOC 1991, 56, 5243.
26. Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. OM 1983, 2, 1694.
27. (a) Uozumi, Y.; Hayashi, T. JACS 1991, 113, 9887. (b) Tamao, K.; Nakajo, E.; Ito, Y. JOC 1987, 52, 957. (c) Roush, W. R.; Grover, P. T. T 1992, 48, 1981.
28. Bergens, S. H.; Noheda, P.; Whelan, J.; Bosnich, B. JACS 1992, 114, 2121.
29. Clark, J. H. CRV 1980, 80, 429.
30. Naso, F.; Ronzini, L. JCS(P1) 1974, 340.
31. Clark, J. H.; Emsley, J. JCS(D) 1975, 2129.
32. Chollet, A.; Hagenbuch, J. P.; Vogel, P. HCA 1979, 62, 511.
33. Lundt, I.; Pedersen, C. S 1992, 669.
34. (a) Wu, W. L.; Chen, S. E.; Chang, W. L.; Chen, C. F.; Lee, A. R. Eur. J. Med. Chem. 1992, 27, 353. (b) González, A. G.; Barrera, J. B.; Hernández, C. Y. H 1992, 34, 1311.
35. Clark, J. H.; Miller, J. M. JACS 1977, 99, 498.
36. Clark, J. H.; Miller, J. M. CC 1976, 229.
37. Reinhoudt, D. N.; Jong, F.; Tomassen, H. P. M. TL 1979, 2067.
38. Halazy, S.; Gross-Bergès, V. CC 1992, 743.
39. Emsley, J.; Hoyte, O. P. A.; Overill, R. E. JACS 1978, 100, 3303.
40. Clark, J. H.; Miller, J. M. TL 1977, 599.
41. Thomas, A.; Manjunatha, S. G.; Rajappa, S. HCA 1992, 75, 715.
42. Apsimon, J. W.; Hooper, J. W.; Laishes, B. A. CJC 1970, 48, 3064.
43. Lawrence, R. W.; Perlmutter, P. CL 1992, 305.
44. Yanami, T.; Kato, M.; Yoshikoshi, A. CC 1975, 726.
45. Rao, A. K. S. B.; Rao, C. G.; Singh, B. B. JCR(S) 1991, 350.
46. Kambe, S.; Yasuda, H. BCJ 1966, 39, 2549.
47. Belsky, I. CC 1977, 237.
48. (a) Kambe, S.; Yasuda, H. BCJ 1968, 41, 1444. (b) Beck, A. K.; Seebach, D. CB 1991, 124, 2897.
49. Rand, L.; Swisher, J. V.; Cronin, C. J. JOC 1962, 27, 3505.
50. Dauben, W. G.; Hart, D. J. JOC 1977, 42, 3787.
51. Clark, J. H.; Miller, J. M. JCS(P1) 1977, 2063.
52. Hatanaka, Y.; Fukushima, S.; Hiyama, T. T 1992, 48, 2113.

Qi Han & Hui-Yin Li

DuPont Merck, Wilmington, DE, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.