Research Brief:
Three Seminal Reactions from the Sharpless Lab
For those interested in the scientific details, here's a closer look
at three seminal discoveries by TSRI's newest Nobel laureate.
Asymmetric
Epoxidation (AE)
Reaction Scheme:
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Facial Selectivity:
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The Asymmetric Epoxidation, or AE, involves the conversion of an allylic
alcohol to an epoxy alcohol. Titanium (IV) isopropoxide is used as a catalyst
and (+) or (-) diethyl or diisopropyl tartrate as a chiral ligand. Use
of a chiral ligand allows t-butyl hydroperoxide to deliver an oxygen stereospecifically
to the olefin, regardless of substitution pattern. Enantiomeric excesses
are generally above 90%, often above 98%. Yields can range from 50% to
99%.
Kinetic Resolution:
With a slight modification of the procedure, it is possible to effect
a kinetic resolution of racemic allylic alcohols.
References:
For the original reference see:
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Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980,
102, 5974. |
For the paper describing kinetic resolution see:
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Martin, V. S.; Woodward, S. S.; Katsuki, T.; Yamada, Y.; Ikeda,
M.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103,
6237. |
For good reviews see:
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Finn, M. G.; Sharpless, K. B. Asymm. Synth. 1985,
5, 247. |
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Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.;
Sharpless, K. B. J. Am. Chem. Soc. 1987, 109,
5765. |
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Asymmetric
Dihydroxylation (AD)
Reaction Scheme:
The Asymmetric Dihydroxylation involves the conversion of a substituted
alkene to a diol. Osmium tetroxide is used as a catalyst and one of the
various cinchona ligands is used to enantioselectively deliver the the
oxygens to the olefin.
Facial Selectivity:
The facial selectivity is easy to predict using a simple mnemonic shown
graphically below.
References:
For the original reference on catalytic AD:
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Jacobsen, E. N.; Marko, I.; Mungall, W. S.; Schroder, G.; Sharpless,
K. B. J. Am. Chem. Soc. 1988, 110, 1968. |
For the original reference on using a two phase system and K3Fe(CN)6
as the oxidant:
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Kwong, H. L.; Sorato, C.; Ogino, Y.; Chen, H.; Sharpless, K. B.
Tetrahedron Lett.1990, 31, 2999. |
For the authoritative review see:
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Kolb, H.; VanNiewenhze, M. S.; Sharpless, K. B. Chem. Rev.1994, 94,
2483-2547. |
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Asymmetric
Aminohydroxylation (AA)
Reaction Scheme:
The Asymmetric Aminohydroxylation involves the conversion of a properly
substituted alkene to an amino alcohol. Osmium tetroxide is used as a
catalyst and one of the various cinchona ligands is used to enantioselectively
deliver the the heteroatoms to the olefin. The cinchona ligands are responsible
for not only enantioselectivity, they also improve regio- and chemoselectivity.
Water is used as an oxygen source, and there are several possible nitrogen
sources.
Selectivity:
The ratio of of the two constitutional isomers is dependant largely on the
substrate, but the regioselectivity can be controlled to a degree by using
the appropriate solvent and ligand. (vide infra) Facial selectivity can
be determined using the simple mnemonic adopted from the AD reaction.
References:
For the original reference see:
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Li, G.; Chang, H.-T.; Sharpless, K. B. Angew. Chem. Int. Ed.
Engl.1996, 35, 451. |
Smaller Nitrogen Sources Are Better:
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Rudolph, J.; Sennhenn, P. C.; Vlarr, C. P.; Sharpless, K. B. Angew.
Chem. Int. Ed. Engl.1996, 35, 2810. |
N-Halocarbamate Salts:
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Li, G.; Angert, H. H.; Sharpless, K. B. Angew. Chem. Int. Ed.
Engl.1996, 35, 2813. |
For good reviews see the following books:
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H. Becker and K. B. Sharpless, Asymmetric Dihydroxylation, in
"Asymmetric Oxidation Reactions: A Practical Approach in Chemistry",
ed. by T. Katsuki, Oxford University Press 2001. |
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H. C. Kolb and K. B. Sharpless, Transition Metals for Fine Chemicals
and Organic Synthesis ed. by M. Beller and C. Bolm, Wiley-VCH
1998. |
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