Osmium Tetroxide-t-Butyl Hydroperoxide1

OsO4-t-BuOOH
(OsO4)

[20816-12-0]  · O4Os  · Osmium Tetroxide-t-Butyl Hydroperoxide  · (MW 254.20) (TBHP)

[75-91-2]  · C4H10O2  · Osmium Tetroxide-t-Butyl Hydroperoxide  · (MW 90.14)

(cis dihydroxylation of alkenes; osmylation)

Physical Data: for 70% aq TBHP: bp 96 °C; mp -2.8 °C; d 0.935 g cm-3. See also Osmium Tetroxide.

Solubility: TBHP: sol acetone, t-butyl alcohol.

Form Supplied in: 70% aq TBHP (remaining water) in plastic bottle.

Handling, Storage, and Precautions: TBHP is an eye and skin irritant. Safety goggles and gloves should be worn when handling TBHP solution. Avoid contamination of high-strength TBHP solution with strong acids and transition metal salts known to be good autooxidation catalysts (e.g. Mn, Fe, and Co). Never work with pure TBHP. Do not distill reaction mixtures containing TBHP without prior reduction with reducing agents such as Na2SO3. Store 70% aq TBHP in plastic containers below 38 °C but not much below 25 °C. Keep away from bright light and heat sources. See also Osmium Tetroxide.

Dihydroxylation of Alkenes.

Although, in some cases, catalytic cis dihydroxylation with OsO4 using Hydrogen Peroxide or metal chlorates as cooxidant gives good yields of diols, over-oxidation leading to high yields of ketols or aldehyde products becomes a problem.1 Thus alkaline t-Butyl Hydroperoxide was introduced as a superior cooxidant in the catalytic cis dihydroxylation. In the OsO4-TBHP system, 70% aq TBHP is normally used and the reaction is usually performed in t-BuOH or acetone when tetraethylammonium acetate (Et4NOAc) is used as the base (see below). In most cases, only 0.2 mol % OsO4 is sufficient for completion of the oxidation.2

The key to the success of the OsO4-TBHP system is the presence of a nucleophile in the form of tetraethylammonium hydroxide (Et4NOH) or Et4NOAc. The role of the nucleophile is to increase the turnover rate of the catalytic cycle by facilitating the hydrolysis of the osmate ester intermediate. For example, it is possible to dihydroxylate even some tetrasubstituted alkenes using the OsO4-TBHP-Et4NOH combination (eq 1).2a

Tetraethylammonium acetate gives higher yields of diol than Et4NOH in the cis dihydroxylation of base-sensitive alkenes even though, as a weaker base, it fails with tetrasubstituted alkenes (eq 2).2b In another example, alkenylphosphonates are dihydroxylated with OsO4-TBHP in acetone in the presence of Et4NOAc to give threo-dihydroxyalkylphosphonates in >80% yields. In contrast, using OsO4-H2O2, a mixture of diol and ketol is obtained.3 The OsO4-TBHP system does not work well in the dihydroxylation of sterically hindered tri- and tetrasubstituted alkenes such as cholesterol (for oxidation of these alkenes, see Osmium Tetroxide-Potassium Ferricyanide).

The OsO4-TBHP system and OsO4-NMO system (see Osmium Tetroxide-N-Methylmorpholine N-Oxide) are quite comparable for the dihydroxylation of simple alkenes. The ability to use less OsO4 and the lower expense of TBHP are the main advantages with the OsO4-TBHP system. However, no asymmetric catalytic dihydroxylation using the OsO4-TBHP system has been developed, and probably due to safety concerns there have been few synthetic applications of the OsO4-TBHP system.3,4

Osmium tetroxide-TBHP is also used for the oxidation of 1-trimethylsilylalkynes to produce a-keto esters in about 60% yield (eq 3). It is most likely that the oxidation involves an a-keto acylsilane which then undergoes a Brook-type rearrangement to the final product.5


1. (a) Sharpless, K. B.; Verhoeven, T. R. Aldrichim. Acta 1979, 12, 63. (b) 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.
2. (a) Sharpless, K. B.; Akashi, K. JACS 1976, 98, 1986. (b) Akashi, K.; Palermo, R. E.; Sharpless, K. B. JOC 1978, 43, 2063.
3. Pondaven-Raphalen, A.; Sturtz, G. PS 1987, 29, 329.
4. (a) Levine, S. G.; Gopalakrishnan, B. TL 1979, 20, 699. (b) Current, S.; Sharpless, K. B. TL 1978, 19, 5075. (c) Kranz, D.; Dinges, K.; Wendling, P. Angew. Makromol. Chem. 1976, 51, 25.
5. Bulman Page, P. C.; Rosenthal, S. TL 1986, 27, 1947.

Yun Gao

Sepracor, Marlborough, MA, USA



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