Osmium Tetroxide-Potassium Ferricyanide1


[20816-12-0]  · O4Os  · Osmium Tetroxide-Potassium Ferricyanide  · (MW 254.20) (K3Fe(CN)6)

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

(cis dihydroxylation of alkenes; asymmetric dihydroxylation of alkenes, enynes, polyenes, and enol ethers)

Physical Data: K3Fe(CN)6: orange crystals, d 1.89 g cm-3. See also Osmium Tetroxide.

Solubility: K3Fe(CN)6: sol water (0.33 g mL-1 at 4 °C, 0.78 g mL-1 at 100 °C); slightly sol alcohol; decomposed by acids.

Handling, Storage, and Precautions: K3Fe(CN)6: wear gloves and goggles. The aqueous solution decomposes slowly on standing. Store away from light. This reagent system should be used in a fume hood. See also Osmium Tetroxide.

Dihydroxylation of Alkenes.

Alkali metal ferricyanides, notably Potassium Ferricyanide, have been used as cooxidants in the studies of OsO4-catalyzed oxidations of lower molecular weight organic compounds.1a For example, propene is dihydroxylated with OsO4-K3Fe(CN)6 in aqueous alkaline solutions to propylene glycol in almost quantitative yield. Potassium ferricyanide and alkali consumed in the reaction have been regenerated electrochemically, resulting in an overall reaction with consumption of alkene, water, and electricity to produce the glycol (eq 1).2

Recently, it has been found that water-insoluble alkenes can be dihydroxylated with the OsO4-K3Fe(CN)6 system in an alkaline aqueous t-BuOH solution to give 1,2-diols in good yields.3 Addition of tertiary amines such as quinuclidine or 1,4-Diazabicyclo[2.2.2]octane (DABCO) accelerates the dihydroxylation with OsO4-K3Fe(CN)6, resulting in an increased yield of diol product. For example, in the presence of DABCO the yield of dihydroxylation of cholesterol increases from 19% to 74%. In this case it appears that DABCO or quinuclidine promotes the hydrolysis of the stable osmate ester intermediate.

The use of K3Fe(CN)6 as a cooxidant for the osmium-catalyzed asymmetric dihydroxylation (AD) in place of N-Methylmorpholine N-Oxide results in across-the-board increases in the level of asymmetric induction for all classes of alkenes.1b,1c The enhanced enantioselectivity is due to the complete suppression of the second cycle observed in the OsO4-NMO system (see Osmium Tetroxide-N-Methylmorpholine N-Oxide) and the use of the t-BuOH-water solvent system, which under the reaction conditions forms a biphasic mixture.4 Both osmium(III) chloride hydrate and potassium osmate(VI) dihydrate [K2OsO4.2H2O] have been used in place of osmium tetroxide. For safety and convenience in handling reasons, potassium osmate is used in the standard set of conditions for the catalytic AD with OsO4-K3Fe(CN)6 and in the commercially available AD mixes.5 Many ligands derived from dihydroquinidine (DHQD) and dihydroquinine (DHQ) have been developed for catalytic AD.1b,6 1,4-Bis(dihydroquinidine) phthalazine ether [(DHQD)2-PHAL] and its diastereomer 1,4-bis(dihydroquinine) phthalazine ether [(DHQ)2-PHAL] have shown significant improvements in enantioselectivity over other ligands for the AD of most alkenes. Polymer-supported DHQD and DHQ derived ligands have been examined for the purpose of recycling of the catalyst.7

For most alkenes, 0.2 mol % of osmium and 1.0 mol % of ligand are sufficient to provide a satisfactory rate of reaction even at 0 °C using 3.0 equiv each of K3Fe(CN)6 and K2CO3. Ready-made mixture containing the four solid components named AD-mix-b (containing (DHQD)2-PHAL) and AD-mix-a (containing (DHQ)2-PHAL) are currently commercially available. Increasing the amount of osmium and ligand and the reaction temperature up to 25 °C can accelerate the AD of more substituted and sterically hindered alkenes.8 In addition, for 1,2-disubstituted, tri- and tetrasubstituted alkenes, addition of up to 3 equiv of sulfonamide (usually methanesulfonamide) enhances the overall rate of the AD by accelerating the hydrolysis of the osmate ester intermediate.5 A mnemonic scheme showing alkene orientation and face selectivity is illustrated in eq 2. However, this mnemonic should be considered as only suggestive of new diol configurations due to the large structural diversity of alkenes.

Table 1 summarizes results of the AD of six types of alkenes using the OsO4-K3Fe(CN)6 system with the preferred DHQD- or DHQ-derived ligands. In general, slightly lower ees are observed in the AD with DHQ-derived ligands than with DHQD-derived ligands.

Besides simple alkenes, enol ethers can be oxidized enantioselectively to give optically active a-hydroxy ketones (eq 3).10

Enynes are dihydroxylated selectively at only the double bond11 and dienes at the more substituted and/or more electron-rich double bond.12 Polyenes such as squalene have been enantioselectively perhydroxylated with OsO4-K3Fe(CN)6 in the presence of (DHQD)2-PHAL or (DHQ)2-PHAL.13 Under buffered condition (in the presence of NaHCO3), even a,b-unsaturated ketones can be dihydroxylated to the corresponding optically active a,b-dihydroxy ketones.14 Kinetic resolution of racemic alkenes have also been reported.15 Diastereoselective dihydroxylation of optically pure alkenes with OsO4-K3Fe(CN)6 in the presence of DHQD- or DHQ-derived ligand results in matched and mis-matched selectivities (also see Osmium Tetroxide). Synthetic transformations of optically pure 1,2-diols to other useful intermediates such as chiral cyclic sulfites, cyclic sulfates,16 and epoxides17 have been developed (eq 4). These new synthetic transformations and the catalytic AD are being increasingly used in the synthesis of optically pure natural products, pharmaceuticals, and other interesting compounds.1,18

1. (a) Singh, H. S. In Organic Synthesis by Oxidation with Metal Compounds, Mijs, W. J.; De Jonge, C. R. H. I., Eds.; Plenum: New York, 1986; Chapter 12. (b) Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis, Ojima, I., Ed.; VCH: New York 1993. (c) Lohray, B. B. TA 1992, 3, 1317.
2. Mayell, J. S. Ind. Eng. Chem., Prod. Res. Dev. 1968, 7, 129.
3. Minato, M.; Yamamoto, K.; Tsuji, J. JOC 1990, 55, 766.
4. (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.
5. Sharpless, K. B.; Amberg, W.; Bennani, Y.; 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.
6. Crispino, G. A.; Jeong, K.-S.; Kolb, H. C.; Wang, Z.-M.; Xu, D.; Sharpless, K. B. JOC 1993, 58, 3785.
7. (a) Kim, B. M.; Sharpless, K. B. TL 1990, 31, 3003. (b) Pini, D.; Petri, A.; Nardi, A.; Rosini, C.; Salvadori, P. TL 1991, 32, 5175. (c) Lohray, B. B.; Thomas, A.; Chittari, P.; Ahuja, J. R.; Dhal, P. K. TL 1992, 33, 5453.
8. Morikawa, K.; Park, J.; Andersson, P. G.; Hashiyama, T.; Sharpless, K. B. JACS 1993, 115, 8463.
9. Wang, L.; Sharpless, K. B. JACS 1992, 114, 7568.
10. Hashiyama, T.; Morikawa, K.; Sharpless, K. B. JOC 1992, 57, 5067.
11. Jeong, K.-S.; Sjö, P.; Sharpless, K. B. TL 1992, 33, 3833.
12. Xu, D.; Crispino, G. A.; Sharpless, K. B. JACS 1992, 114, 7570.
13. (a) Crispino, G. A.; Sharpless, K. B. TL 1992, 33, 4273. (b) Crispino, G. A.; Ho, P. T.; Sharpless, K. B. Science 1993, 259, 64.
14. Walsh, P. J.; Sharpless, K. B. SL 1993, 8, 605.
15. (a) Ward, R. A.; Procter, G. TL 1992, 33, 3363. (b) Lohray, B. B. TA 1992, 3, 1317. (c) Lohray, B. B.; Bhushan, V. TL 1993, 34, 3911. (d) VanNieuwenhze, M. S.; Sharpless, K. B. JACS 1993, 115, 7864.
16. (a) Gao, Y.; Sharpless, K. B. JACS 1988, 110, 7538. (b) For review, see Lohray, B. B. S 1992, 1035.
17. Kolb, H. C.; Sharpless, K. B. T 1992, 48, 10515.
18. (a) Sinha, S. C.; Keinan, E. JACS 1993, 115, 4891. (b) Rao, A. V. R.; Rao, S. P.; Bhanu, M. N. CC 1992, 859. (c) Keinan, E.; Sinha, S. C.; Sinha-Bagchi, A.; Wang, Z.-M.; Zhang, X.-L.; Sharpless, K. B. TL 1992, 33, 6411. (d) Bennani, Y. L.; Sharpless, K. B. TL 1993, 34, 2083.

Yun Gao

Sepracor, Marlborough, MA, USA

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