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Vicinal Syn Dihydroxylation

Osmium tetroxide oxidizes alkenes to give glycols through syn addition. A glycol, also known as a vicinal diol, is a compound with two -OH groups on adjacent carbons. 

glycol.bmp

Introduction

The reaction with \(OsO_4\) 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. 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.

Cis alkenes.bmp

\(OsO_4\) is formed slowly when osmium powder reacts with gasoues \(O_2\) at ambient temperature. Reaction of bulk solid requires heating to 400 °C:

\[Os_{(s)} + 2O_{2\;(g)} \rightarrow OS_4\]

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, \(KMnO_4\). 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

example.bmp

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.

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.

Problem 1 (1).bmp

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

 Problem 2.bmp

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

Problem 3.bmp

4. Draw the intermediate of this reaction.

Problem 4.bmp

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

Problem 5.bmp

 

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.

Answer 1.bmp

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

Answer 2.bmp

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

Answer 3.bmp

4. A cyclic osmic ester is formed.

Answer 4.bmp

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.

Answer 5.bmp

Contributors

  • Shivam Nand