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Related Reactions
Sharpless Epoxidation
Sharpless Oxyamination
Upjohn Dihydroxylation
Synthesis of 1,2-diols

Sharpless Dihydroxylation

The Sharpless Dihydroxylation or Bishydroxylation is used in the enantioselective preparation of 1,2-diols from prochiral olefins. This procedure is performed with an osmium catalyst and a stoichiometric oxidant [e.g. K3Fe(CN)6 or N-methylmorpholine oxide (NMO)]; it is carried out in a buffered solution to ensure a stable pH, since the reaction proceeds more rapidly under slightly basic conditions. Enantioselectivity is achieved through the addition of enantiomerically-enriched chiral ligands [(DHQD)2PHAL, (DHQ)2PHAL or their derivatives]. These reagents are also available as stable, prepackaged mixtures (AD-mix α and AD-mix β, AD = asymmetric dihydroxylation) for either enantiopreference.

Mechanism of the Sharpless Dihydroxylation

The ligand accelerates the reaction and transfers the chiral information.

After the dihydroxylated product is released from the complex through hydrolysis, reoxidation of the metal takes place - sodium chlorite is used in this example, which can regenerate two equivalents of the catalyst.

M. H. Junttila, O. E. O. Hormi, J. Org. Chem., 2004, 69, 4816-4820.

If the olefin concentration is too high, a second equivalent of the substrate might bind to the catalytic center in the absence of the chiral ligand, and undergo a dihydroxylation. This side reaction will decrease the enantioselectivity.

There has been some speculation regarding the actual addition step, for which experimental data suggest the possible involvement of two separate steps. Thus, the question arises during these discussions of whether the key step takes place via an initial [3+2]-addition, or by a [2+2]-addition followed by expansion of the metallacycle.

Quantum chemical calculations have shown an initial [3+2]-addition of the OsO4 to be energetically more favorable. However, this energy difference is substantially smaller in the related Re(VII) oxide additions, for example. (D. V. Deubel, G. Frenking, Acc. Chem. Res., 2003, 36, 645. DOI).

Recent Literature

Catalytic Asymmetric Dihydroxylation of Olefins with Reusable OsO42- on Ion-Exchangers: The Scope and Reactivity Using Various Cooxidants
B. M. Choudary, N. S. Chodari, K. Jyothi, M. L. Kantam, J. Am. Chem. Soc., 2002, 124, 5341-5349.

Methanesulfonamide: a Cosolvent and a General Acid Catalyst in Sharpless Asymmetric Dihydroxylations
M. H. Junttila, O. O. E. Hormi, J. Org. Chem., 2009, 74, 3038-3047.

Sodium Chlorite as an Efficient Oxidant and Hydroxy Ion Pump in Osmium-Catalyzed Asymmetric Dihydroxylation
M. H. Junttila, O. E. O. Hormi, J. Org. Chem., 2004, 69, 4816-4820.

Ionic Liquids as a Convenient New Medium for the Catalytic Asymmetric Dihydroxylation of Olefins Using a Recoverable and Reusable Osmium/Ligand
L. C. Branco, C. A. M. Afonso, J. Org. Chem., 2004, 69, 4381-4389.

A New Practical Method for the Osmium-Catalyzed Dihydroxylation of Olefins­ using Bleach as the Terminal Oxidant
G. M. Mehltretter, S. Bhor, M. Klawonn, C. Döbler, U. Sundermeier, M. Eckert, H.-C. Militzer, M. Beller, Synthesis, 2003, 295-301.