Sharpless asymmetric dihydroxylation


Sharpless asymmetric dihydroxylation

Sharpless asymmetric dihydroxylation (also called the Sharpless bishydroxylation) is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol.[1][2][3]

The Sharpless dihydroxylation.
RL = Largest substituent; RM = Medium-sized substituent; RS = Smallest substituent

It is common practice to perform this reaction using a catalytic amount of osmium tetroxide, which after reaction is regenerated with either potassium ferricyanide[4][5] or N-methylmorpholine N-oxide.[6][7] This dramatically reduces the amount of the highly toxic and very expensive osmium tetroxide needed. These four reagents are commercially available premixed ("AD-mix") The mixture containing (DHQ)2-PHAL is called AD-mix-α, and the mixture containing (DHQD)2-PHAL is called AD-mix-β.[8]

Such chiral diols are important in organic synthesis. The introduction of chirality into nonchiral reactants through usage of a chiral catalysts is an important concept in organic synthesis. This reaction was developed principally by K. Barry Sharpless building on the already known racemic Upjohn dihydroxylation, for which he was awarded a share of the 2001 Nobel Prize in Chemistry.

Contents

Reaction mechanism

The reaction mechanism of the Sharpless dihydroxylation begins with the formation of the osmium tetroxide - ligand complex (2). A [3+2]-cycloaddition with the alkene (3) gives the cyclic intermediate 4.[9][10] Basic hydrolysis liberates the diol (5) and the reduced osmate (6). Finally, the stoichiometric oxidant regenerates the osmium tetroxide - ligand complex (2).

The reaction mechanism of the Sharpless dihydroxylation

Application

Dihydroxylation in the absence of a coordinating ligand requires the use of a stoichiometric amount of osmium.[11][12][13] Catalytic, asymmetric dihydroxylation reduces the cost of this procedure one thousandfold, opening the door for advances in biomimetic and sympathetic osmates.

Asymmetric dihydroxylation has been applied to alkenes of every substitution, and high enantioselectivities have been realized for every substitution pattern. Asymmetric dihydroxylation reactions are also highly site selective, providing products derived from reaction of the most electron-rich double bond in the substrate.[14]

Examples

Synthesis of azasugars using the Sharpless asymmetric dihydroxylation

The first step in the synthesis of azasugar 6 is a dihydroxylation reaction[15] of the prochiral diene 1. Azasugars are pharmacologically relevant. The entire reaction sequence takes place in water as a reaction medium and protective groups were not required. Notice the chemoselectivity in the nucleophilic substitution of bromine by the hydroxyl group in step 2.

For another example of this reaction see: Kuwajima Taxol total synthesis

References

  1. ^ Jacobsen, E. N.; Marko, I.; Mungall, W. S.; Schroeder, G.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 1968. (doi:10.1021/ja00214a053)
  2. ^ Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483-2547. (Review) (doi:10.1021/cr00032a009)
  3. ^ Gonzalez, J.; Aurigemma, C.; Truesdale, L. Org. Syn., Coll. Vol. 10, p.603 (2004); Vol. 79, p.93 (2002). (Article)
  4. ^ Minato, M.; Yamamoto, K.; Tsuji, J. J. Org. Chem. 1990, 55, 766-768. (doi:10.1021/jo00289a066)
  5. ^ Oi, R.; Sharpless, K. B. Org. Syn., Coll. Vol. 9, p.251 (1998); Vol. 73, p.1 (1996). (Article)
  6. ^ VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 1973-1976.
  7. ^ McKee, B. H.; Gilheany, D. G.; Sharpless, K. B. Org. Syn., Coll. Vol. 9, p.383 (1998); Vol. 70, p.47 (1992). (Article)
  8. ^ Sharpless, K. B., et al. J. Org. Chem. 1992, 57, 2768-2771. (doi:10.1021/jo00036a003)
  9. ^ Corey, E.J.; Noe, M. C.; Grogan, M. J. Tetrahedron Lett. 1996, 37, 4899-4902.
  10. ^ DelMonte, A. J.; Haller, J.; Houk, K. N.; Sharpless, K. B.; Singleton, D. A.; Strassner, T.; Thomas, A. A. J. Am. Chem. Soc. 1997, 119, 9907-9908. (doi:10.1021/ja971650e)
  11. ^ Jacobsen, E. N.; Marko, I.; Mungall, W. S.; Schroeder, G.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 1968. (doi:10.1021/ja00214a053)
  12. ^ Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483-2547. (Review) (doi:10.1021/cr00032a009)
  13. ^ Gonzalez, J.; Aurigemma, C.; Truesdale, L. Org. Syn., Coll. Vol. 10, p.603 (2004); Vol. 79, p.93 (2002). (Article)
  14. ^ Noe, M. C.; Letavic, M. A.; Snow, S. L. Org. React. 2005, 66, 109. (doi:10.1002/0471264180.or066.02)
  15. ^ Efficient asymmetric synthesis of an azasugar in water Ulf M. Lindström, Rui Ding, Olle Hidestål Chemical Communications 2005, 1773.

See also


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Asymmetric catalytic oxidation — is a technique of oxidizing various substrates to give an enantiopure product using a catalyst.Reactions*Jacobsen epoxidation of alkenes using manganese salen complex and NaOCl *Sharpless epoxidation of allyl alcohols using titanium isopropoxide …   Wikipedia

  • Upjohn dihydroxylation — is an organic reaction converting an alkene to a cis vicinal diol, and was developed by V. VanRheenen, R. C. Kelly and D. Y. Cha of the Upjohn Company, USA in 1976. [V. VanRheenen, R. C. Kelly and D. Y. Cha Tetrahedron Lett. 1976, 1973 1976.… …   Wikipedia

  • Karl Barry Sharpless — Infobox Scientist name = Karl Barry Sharpless image size = 180px birth date = birth date and age|1941|04|28|df=yes birth place = Philadelphia, Pennsylvania, USA nationality = United States field = Chemistry work places = alma mater = Stanford… …   Wikipedia

  • Osmium tetroxide — Osmium tetroxide …   Wikipedia

  • AD-mix — in organic chemistry is a commercially available mixture of reagents for performing amongst others the Sharpless asymmetric dihydroxylation of alkenes. The mix is available in two variations, AD mix α and AD mix β following ingredient lists… …   Wikipedia

  • Osmium — This article is about the chemical element. For other uses, see Osmium (disambiguation). rhenium ← osmium → iridium Ru ↑ Os ↓ Hs …   Wikipedia

  • List of organic reactions — Well known reactions and reagents in organic chemistry include Contents: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z    See also   Ext …   Wikipedia

  • Milas hydroxylation — The Milas hydroxylation is an organic reaction converting an alkene to a vicinal diol, and was developed by N. A. Milas in the 1930s.[1] The cis diol is formed by reaction of alkenes with hydrogen peroxide and either ultraviolet light or a… …   Wikipedia

  • AD (disambiguation) — AD and Ad may refer to: *Anno Domini, Latin for In the Year of (Our) Lord , applied to years in the proleptic Gregorian calendar following 1 BC. *Advertisement, the promotion of an item, service, company, and/or ideaMedia and culture* , a… …   Wikipedia

  • Lemieux-Johnson oxidation — The Lemieux Johnson oxidation is a chemical reaction named after its discoverers, R. U. Lemieux and W. S. Johnson, who published it in 1956. [cite journal author = Pappo, R.; Allen, D. S., Jr.; Lemieux, R. U.; Johnson, W. S. title = Osmium… …   Wikipedia


Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.