Sharpless asymmetric dihydroxylation
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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 diol.<ref>Jacobsen, E. N.; Marko, I.; Mungall, W. S.; Schroeder, G.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 1968. (DOI:10.1021/ja00214a053)</ref><ref>Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483-2547. (Review) (DOI:10.1021/cr00032a009)</ref><ref>Gonzalez, J.; Aurigemma, C.; Truesdale, L. Org. Syn., Coll. Vol. 10, p.603 (2004); Vol. 79, p.93 (2002). (Article)</ref>
It is common practice to perform this reaction using a catalytic amount of osmium tetroxide, which after reaction is regenerated with either potassium ferricyanide<ref>Minato, M.; Yamamoto, K.; Tsuji, J. J. Org. Chem. 1990, 55, 766-768. (DOI:10.1021/jo00289a066)</ref><ref>Oi, R.; Sharpless, K. B. Org. Syn., Coll. Vol. 9, p.251 (1998); Vol. 73, p.1 (1996). (Article)</ref> or N-methylmorpholine N-oxide<ref>VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 1973-1976.</ref><ref>McKee, B. H.; Gilheany, D. G.; Sharpless, K. B. Org. Syn., Coll. Vol. 9, p.383 (1998); Vol. 70, p.47 (1992). (Article)</ref>. This dramatically reduces the amount of the highly toxic and very expensive osmium tetroxide needed. These four reagents are commercially available premixed.<ref>Sharpless, K. B., et al. J. Org. Chem. 1992, 57, 2768-2771. (DOI:10.1021/jo00036a003)</ref> The mixture containing (DHQ)2-PHAL is called AD-mix-α, and the mixture containing (DHQD)2-PHAL is called AD-mix-β.
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, for which he was awarded a share of the 2001 Nobel Prize in Chemistry.
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[edit] Quinine ligands
- For more details on this topic, see AD-mix.
Both are C2-symmetric, pseudo-enantiomeric ligands.
[edit] Reaction mechanism
The reaction mechanism of the Sharpless dihdyroxylation begins with the formation of the osmium tetroxide - ligand complex (2). A [3+2]-cycloaddition with the alkene (3) gives the cyclic intermediate 4.<ref>Corey, E.J.; Noe, M. C.; Grogan, M. J. Tetrahedron Lett. 1996, 37, 4899-4902.</ref><ref>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)</ref> Basic hydrolysis liberates the diol (5) and the reduced osmate (6). Finally, the stoichiometric oxidant regenerates the osmium tetroxide - ligand complex (2).
[edit] Examples
The first step in the synthesis of azasugar 6 is a dihydroxylation reaction<ref>Efficient asymmetric synthesis of an azasugar in water Ulf M. Lindström, Rui Ding, Olle Hidestål Chemical Communications 2005, 1773.</ref> 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.
[edit] References
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