Introduction

The reaction with OsO₄ is a concerted process that has a cyclic intermediate and no rearrangements. Vicinal syn dihydroxylation complements the epoxide-hydrolysis sequence which constitutes an anti dihydroxylation of an alkene (section 12-10). When an alkene reacts with osmium tetroxide, stereocenters can form in the glycol product. Cis alkenes give meso products and trans alkenes give racemic mixtures.

OsO₄  is prepared by the reaction of Os + 2O₂. Since Osmium tetroxide is expensive and highly toxic, the reaction with alkenes has been modified. Catalytic amounts of OsO₄ and stoichiometric amounts of an oxidizing agent such as hydrogen peroxide are now used to eliminate some hazards. Also, an older reagent that was used instead of OsO₄ was potassium permanganate, KMnO₄. Although syn diols will result from the reaction of KMnO₄ and an alkene, potassium permanganate is less useful since it gives poor yields of the product because of overoxidation. 

Mechanism

• Electrophilic attack on the alkene
  • Pi bond of the alkene acts as the nucleophile and reacts with osmium (VIII) tetroxide (OsO₄) 
  • 2 electrons from the double bond flows toward the osmium metal
    • In the process, 3 electron pairs move simultaneously
  • Cyclic ester with Os (VI) is produced
• Reduction
  • H₂S reduces the cyclic ester
    • NaHSO₄ with H₂O may be used 
  • Forms the syn-1,2-diol (glycol)

Example: Dihydroxylation of 1-ethyl-1-cycloheptene

Chemical Highlight

Antitumor drugs have been formed by using dihydroxylation. This method has been applied to the enantioselective synthesis of ovalicin, which is a class of fungal-derived products called antiangiogenesis agents. These antitumor products can cut off the blood supply to solid tumors. A derivative of ovalicin, TNP-470, is chemically stable, nontoxic, and noninflammatory. TNP-470 has been used in research to determine its effectiveness in treating cancer of the breast, brain, cervix, liver, and prostate.

Outside links

• http://en.wikipedia.org/wiki/Osmium_tetroxide
• http://www.chm.bris.ac.uk/motm/oso4/oso4v.htm
• http://www.organic-chemistry.org/chemicals/oxidations/osmiumtetroxide.shtm

References

1. Dehestani, Ahmad et al. (2005). Ligand-assisted reduction of osmium tetroxide with molecular hydrogen via a [3+2] mechanism. Journal     of the American Chemical Society, 2005, 127 (10), 3423-3432.
2. Sorrell, Thomas, N. Organic Chemistry. New York: University Science Books, 2006.
3. Vollhardt, Peter, and Neil E. Schore. Organic Chemistry: Structure and Function. 5th Edition. New York: W. H. Freeman & Company, 2007.

Problems

Questions:

1. Give the major product.

2. What is the product in the dihydroxylation of (Z)-3-hexene?

3. What is the product in the dihydroxylation of (E)-3-hexene?

4. Draw the intermediate of this reaction.

5. Fill in the missing reactants, reagents, and product.

Answers:

1. A syn-1,2-ethanediol is formed. There is no stereocenter in this particular reaction. The OH groups are on the same side.

2. Meso-3,4-hexanediol is formed. There are 2 stereocenters in this reaction.

3. A racemic mixture of 3,4-hexanediol is formed. There are 2 stereocenters in both products.

4. A cyclic osmic ester is formed.

5. The Diels-Alder cycloaddition reaction is needed in the first box to form the cyclohexene. The second box needs a reagent to reduce the intermediate cyclic ester (not shown). The third box has the product: 1,2-cyclohexanediol.

Contributors

• Shivam Nand

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