Reagent Friday: OsO4 (Osmium Tetroxide)
Last updated: January 29th, 2020 |
OsO4 (Osmium Tetroxide) As A Reagent For the Dihydroxylation Of Alkenes
In a blatant plug for the Reagent Guide, each Friday I profile a different reagent that is commonly encountered in Org 1/ Org 2.
Today’s reagent is among one of the best and most useful at what it does in all of organic chemistry. It’s blindingly good, in fact. So blinding, I don’t know if I’ve ever seen an example of it being used in an undergraduate teaching lab. It’s not a reagent for rookies: it’s genuinely dangerous, and should be handled with extreme care.
OsO4 For The Formation Of Vicinal Diols From Alkenes
Osmium tetroxide (OsO4) is a volatile liquid that is most useful for the synthesis of 1,2 diols from alkenes. (Side note: another name for 1,2 diols is vicinal diols, or vic-diols). The reaction is very mild, and usefully leads to the formation of syn diols. Another side note: this reaction doesn’t work with alkynes.
Alkene Dihydroxylation With Osmium Tetroxide (OsO4): How It Works
The reaction works through a concerted process whereby two oxygens from the osmium interact with one face of the double bond. This results in a 5-membered ring (called an osmate ester) and generates the syn stereochemistry. The osmate ester is broken up into the 1,2-diol by use of an aqueous solution of a reducing agent such as potassium bisulfite, KHSO3. This is frequently omitted in textbooks (the mechanism is tedious to write out), but is worth mentioning just in case.
By the way, dihydroxylation of alkenes can also be performed with cold, dilute potassium permanganate (KMnO4). One advantage of OsO4 is that it is much more compatible with other functional groups than KMnO4, which is kind of a ravenous beast.
Why is osmium “blindingly good”? One of the molecules required for vision is retinol:
What do you think would happen if the vapors from OsO4 reached your eyes? Everything would go dark, let me tell you.
The good news is that apparently the blindness wears off after several months.
P.S. You can read about the chemistry of OsO4 and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF.
P.P.S. One preparation in Woodward’s synthesis of cortisone (subscription req’d) calls for Osmium tetroxide (68.48 g) . Talk about courage!!!
(Advanced) References and Further Reading
- Oxydation ungesättigter Verbindungen mittels organischer Superoxyde
Nikolaus Prileschajew. Chemische Berichte, 1909, 42, 4811. DOI: 10.1002/cber.190904204100
This reaction (epoxidations of alkenes with a peracid) is also known as the Prizelhaev reaction after the author.
- The oxidation of olefins with perbenzoic acids. A kinetic study
M. Lynch and K. H. Pausacker. J. Chem. Soc. 1955, 1525-1531. DOI: 10.1039/JR9550001525
One of the earliest papers on epoxidation with m-CPBA, comparing its reactivity with other substituted peracids. As expected, the reactivity of peroxyacids is increased by electron-withdrawing groups.
- m-CHLOROPERBENZOIC ACID
Richard N. McDonald, Richard N. Steppel, and James E. Dorsey. Synth. 1970, 50, 15. DOI: 10.15227/orgsyn.050.0015
A reliable preparation for m-CPBA (which is commercially available) in Organic Syntheses. As this procedure shows, m-CPBA is not prepared as a pure compound (it is a mixture of the peracid and acid, and commercial samples may contain residual water for stability).
- Epoxidations with m-Chloroperbenzoic Acid
Nelson N. Schwartz and John H. Blumbergs. J. Org. Chem. 1964 29, (7), 1976-1979. DOI: 1021/jo01030a078
This paper describes mechanistic studies of m-CPBA oxidation that demonstrate that ionic intermediates are not involved in the reaction, and that the rate is insensitive to solvent polarity.
- Record of chemical progress
Bartlett, P. D. Chem. Prog. 1950, 11, 47
This is the publication in which Prof. P. D. Bartlett describes the ‘butterfly mechanism’ for m-CPBA epoxidation.
- MCPBA Epoxidation of Alkenes: Reinvestigation of Correlation between Rate and Ionization Potential
Cheal Kim, Teddy G. Traylor, and Charles L. Perrin. J. Am. Chem. Soc. 1998, 120, (37), 9513-9516. DOI: 1021/ja981531e
An interesting paper that describes the development of a kinetic method for measuring the rate of epoxidation of various alkenes with m-CPBA.
- Experimental Geometry of the Epoxidation Transition State
Daniel A. Singleton, Steven R. Merrigan, Jian Liu, and K. N. Houk. J. Am. Chem. Soc. 1997, 119, (14), 3385-3386. DOI: 1021/ja963656u
Combined experimental and theoretical studies of the epoxidation transition state, showing that both C-O bond forming events are nearly synchronous.
- The mechanism of epoxidation of olefins by peracids
V. G. Dryuk. Tetrahedron. Volume 32, Issue 23, 1976, 2855-2866. DOI:10.1016/0040-4020(76)80137-8
An account of the author’s work on kinetic studies of the epoxidation of olefins with peracids in order to determine the exact mechanism.