Potassium Ferricyanide1


[13746-66-2]  · C6FeK3N6  · Potassium Ferricyanide  · (MW 329.27)

(mild oxidizing agent for functional groups;1 capable of oxidative coupling of phenols;2 can function as reoxidant in osmium-catalyzed asymmetric dihydroxylation of alkenes3)

Alternate Name: potassium hexacyanoferrate(III).

Physical Data: d 1.890 g cm-3.

Solubility: sol 33 g/100 ml in cold water, 77.5 g/100 ml in hot water; insol alcohol.

Form Supplied in: orange crystalline solid; widely available.

Handling, Storage, and Precautions: stable in air; light sensitive. Aqueous solutions decompose slowly on standing. Contact with strong acid liberates highly toxic gas. Avoid contact with skin and eyes. Avoid breathing dust. Use in a fume hood.

Functional Group Oxidations.

K3Fe(CN)6, a one-electron oxidant, is often used in an alkaline solution with an organic solvent. Since it is soluble in the aqueous phase but insoluble in most organic solvents, the reaction can be easily worked up by simple aqueous extraction. K3Fe(CN)6 has been reported to oxidize quaternary ammonium salts to pyridones,4 acyloins to diketones,5 and 3,4-disubstituted 4-halo-2-pyrazolin-5-ones to disubstituted alkynes (eq 1).6 Demethylation has been reported for certain tertiary amines,7 while diacids have been shown to undergo decarboxylation.8

Oxidative Coupling of Phenols.

One of the most important uses of K3Fe(CN)6 is the oxidation of phenols. Stable aroxyl radicals can be prepared by reacting 2,4,6-trisubstituted phenols with alkaline K3Fe(CN)6 (eq 2).9 With appropriate substituents, the dimer product from intermolecular oxidative coupling can be obtained in good yield (eqs 3 and 4).10,11

A stereospecific and stereoselective oxidative coupling of a chiral tetrahydronaphthol using K3Fe(CN)6 has also been demonstrated (eq 5).12

K3Fe(CN)6 has been used extensively for intramolecular oxidative coupling of phenolic substrates,2 often with remarkably high yields (eqs 6 and 7).13,14

Other oxidants that have been commonly used for oxidative phenolic coupling are Iron(III) Chloride, Iron(III) Chloride-Silica Gel, Manganese Dioxide, Lead(IV) Oxide, Mercury(II) Oxide, Silver(II) Oxide, Phenyliodine(III) Bis(trifluoroacetate), Thallium(III) Trifluoroacetate, ruthenium trifluoroacetate, Vanadyl Trichloride, and Vanadyl Trifluoride.2 For the oxidation of a phenolic b-diketone, K3Fe(CN)6 gives the coupling product in very good yield (eq 8),15 while several other oxidants (e.g. FeCl3, VOF3, VOCl3, Copper(II) Chloride) were unsuccessful. However, VOCl3 has been shown to be superior to K3Fe(CN)6 in the oxidation of a diphenolic substrate (eq 9).16

K3Fe(CN)6 has also been used in the synthesis of hydroxyindoles by the oxidation of suitably substituted hydroquinones.17

As Reoxidant in Osmium-Catalyzed Dihydroxylation.

Another very important use of alkaline potassium ferricyanide is as a stoichiometric reoxidant in the osmium-catalyzed dihydroxylation of alkenes to give diols (eq 10).18 Sodium sulfite is usually added to the reaction mixture to quench the excess ferricyanide before work-up.

Other co-oxidants, such as sodium or potassium chlorate,19 Hydrogen Peroxide in t-butyl alcohol,20 t-Butyl Hydroperoxide under alkaline conditions,21 and amine N-oxides,22 have also been used for this purpose. Although catalytic cis-dihydroxylation using perchlorates or hydrogen peroxide usually gives good yield of diol, over-oxidation is difficult to avoid. Both K3Fe(CN)6 and N-Methylmorpholine N-Oxide (NMO) have proven to be very mild and effective co-oxidants. However, K3Fe(CN)6 has been shown to be the most efficient oxidant in the osmium-catalyzed asymmetric dihydroxylation of prochiral alkenes with derivatives of dihydroquinidine (DHQD) and dihydroquinine (DHQ) as chiral ligands to give chiral diols. The use of this oxidant precludes the second cycle which gives very low enantioselectivity and leads to enantioselectivities not obtainable with the use of other oxidants (eqs 11 and 12).23

Related Reagents.

Osmium Tetroxide; Osmium Tetroxide-Potassium Ferricyanide.

1. Thyagarajan, B. S. CRV 1958, 58, 439.
2. (a) Oxidative Coupling of Phenols; Taylor, W. I.; Battersby, A. R., Eds.; Dekker: New York, 1967. (b) For reviews of aryl-aryl bond formation, see Sainsbury, M. T 1980, 36, 3327. (c) Bringmann, G.; Walter, R.; Weirich, R. AG(E) 1990, 29, 977.
3. (a) Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: Weinheim, 1993; pp 227-272. (b) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J.; Jeong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L. JOC 1992, 57, 2768. (c) Crispino, G. A.; Jeong, K.-S.; Kolb, H. C.; Wang, Z.-M.; Xu, D.; Sharpless, K. B. JOC 1993, 58, 3785. (d) Sharpless, K. B.; Amberg, W.; Beller, M.; Chen, H.; Hartung, J.; Kawanami, Y.; Lübben, D.; Manoury, E.; Ogino, Y.; Shibata, T.; Ukita, T. JOC 1991, 56, 4585.
4. Prill, E. A.; McElvain, S. M. OSC 1943, 2, 419.
5. El-Zaru, R. A.; Jarrar, A. A. CI(L) 1977, 741.
6. Kocienski, P. J.; Ansell, J. M.; Norcross, B. E. JOC 1976, 41, 3650.
7. Perrine, T. D. JOC 1951, 16, 1303.
8. (a) Lohaus, H. LA 1935, 516, 295. (b) McDonald, R. N.; Campbell, T. W. JOC 1959, 24, 1969. (c) Campbell, T. W.; McDonald, R. N. OSC 1973, 5, 985.
9. Müller, E.; Schick, A.; Mayer, R.; Scheffler, K. CB 1960, 93, 2649.
10. Hewgill, F. R. T 1978, 34, 1595.
11. Butenandt, A.; Schiedt, U.; Biekert, E. LA 1954, 588, 106.
12. (a) Feringa, B.; Wynberg, H. JACS 1976, 98, 3372. (b) Feringa, B.; Wynberg, H. JOC 1981, 46, 2547.
13. (a) Taub, D.; Kuo, C. H.; Slates, H. L.; Wendler, N. L. T 1963, 19, 1. (b) Taub, D.; Kuo, C. H.; Wendler, N. L. JOC 1963, 28, 2752.
14. McDonald, E.; Suksamrarn, A. TL 1975, 4421.
15. Kende, A. S.; Ebetino, F. H.; Ohta, T. TL 1985, 26, 3063.
16. Schwartz, M. A.; Rose, B. F.; Holton, R. A.; Scott, S. W.; Vishnuvajjala, B. JACS 1977, 99, 2571.
17. Harley-Mason, J.; Jackson, A. H. JCS 1954, 3651.
18. Minato, M.; Yamamoto, K.; Tsuji, J. JOC 1990, 55, 766.
19. (a) Hofmann, K. A. CB 1912, 45, 3329. (b) Hofmann, K. A.; Ehrhart, O.; Schneider, O. CB 1913, 46, 1657.
20. (a) Milas, N. A.; Sussman, S. JACS 1936, 58, 1302. (b) Milas, N. A.; Sussman, S. JACS 1937, 59, 2345. (c) Milas, N. A.; Trepagnier, J. H.; Nolan, J. T. Jr.; Iliopulos, M. I. JACS 1959, 81, 4730.
21. (a) Sharpless, K. B.; Akashi, K. JACS 1976, 98, 1986. (b) Akashi, K.; Palermo, R. E.; Sharpless, K. B. JOC 1978, 43, 2063.
22. (a) VanRheenen, V.; Kelly, R. C.; Cha, D. Y. TL 1976, 23, 1973. (b) Ray, R.; Matteson, D. S. TL 1980, 21, 449.
23. (a) Kwong, H.-L.; Sorato, C.; Ogino, Y.; Chen, H.; Sharpless, K. B. TL 1990, 31, 2999. (b) Ogino, Y.; Chen, H.; Kwong, H.-L.; Sharpless, K. B. TL 1991, 32, 3965. (c) Wai, J. S. M.; Markó, I.; Svendsen, J. S.; Finn, M. G.; Jacobsen, E. N.; Sharpless, K. B. JACS 1989, 111, 1123.

Hoi-Lun Kwong

Harvard University, Cambridge, MA, USA

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