Kinetic resolution
From Wikipedia, the free encyclopedia
In kinetic resolution two enantiomers show different reaction rates in a chemical reaction thereby creating an excess of the less reactive enantiomer [1]. This excess goes through a maximum and disappears on full completion of the reaction. Kinetic resolution is a very old concept in organic chemistry and can be used in the organic synthesis of chiral molecules. It has been surpassed by other methods.
Kinetic resolution was first observed by Marckwald and McKenzie in 1899 [2] in the esterfication reaction of racemic mandelic acid with optically active (-)-menthol to a pair of diastereomeric esters.
In this reaction the (R)-enantiomer of mandelic acid displays the higher reaction rate and with incomplete conversion the reaction mixture gets enriched in (S)-mandelic acid. Full hydrolysis of the incomplete mixture of esters gives an excess of (R)-mandelic acid. Taking the reaction to 100% completion will again produce equal amounts of both esters.
Contents |
[edit] Dynamic kinetic resolution
An important extension of kinetic resolution is called dynamic kinetic resolution or DKR for short. It tackles the obvious drawbacks of the above described system that the maximum conversion in the reaction is only 50% and that the product has to be separated from the reactants. In DKR it is possible to convert the achiral reactant with 100% completion because both (reactant) enantiomers form a chemical equilibrium and exchange. In this way the faster reacting enantiomer is replenished in the course of the reaction at the expense of the slower reacting enantiomer. The observed dynamics are based on the Curtin-Hammett principle.
One of the earliest demonstrations of this method [3]is an adaptation of the Noyori asymmetric hydrogenation by Ryoji Noyori:
The enantiomers interconvert through their common enol. The ultimate reaction product is the protected syn adduct l-threonine (2S,3R) with 99% diastereomeric excess (preference for the syn diastereomeric pair and not the anti pair) and 99% enantiomeric excess (preference 3R product within syn-pair).
[edit] Mutual and Parallel Kinetic resolution
Mutual kinetic resolution (MKR) is the reaction between two sets of racemic compounds via a kinetic pathway. The reason for the kinetic resolution to be described as a "mutual" kinetic resolution is due to the mutual reaction between the two sets of racemates.
Parallel kinetic resolution (PKR) is much the same as mutual kinetic resolution except that, instead of using two sets of racemates, only one set of racemates is used and resolved using a pseudo-enantiomeric mixture of reagents.
[edit] See also
| Concepts in asymmetric synthesis | |
|---|---|
| Analysis: | Optical rotation, Enantiomeric excess, Diastereomeric excess, Chiral derivitizing agents |
| Chiral resolution: | Crystallization, Kinetic resolution, Chiral column chromatography |
| Reactions: | Asymmetric induction, Chiral reagents, Chiral pool synthesis, Chiral auxiliaries, Asymmetric catalytic reduction, Asymmetric catalytic oxidation, Organocatalysis, Biocatalysis |
[edit] External links
- Dynamic chiral resolutions A MacMillan Group Meeting Jake Wiener Link
- Dynamic Kinetic Resolution:A Powerful Approach to Asymmetric Synthesis Erik Alexanian Supergroup Meeting March 30, 2005 Link
- Dynamic Kinetic Resolution: Practical Applications in Synthesis Valerie Keller 3rd Year Seminar November 1, 2001 Link
[edit] References
- ^ Asymmetric Synthesis of Natural Products, Ari Koskinen ISBN 0-471-93848-3
- ^ W. Marckwald, A. McKenzie, Ber. Dtsch. Chem. Ges. 1899
- ^ Stereoselective hydrogenation via dynamic kinetic resolution R. Noyori, T. Ikeda, T. Ohkuma, M. Widhalm, M. Kitamura, H. Takaya, S. Akutagawa, N. Sayo, T. Saito, and et al. J. Am. Chem. Soc.; 1989; 111(25) pp 9134 - 9135; DOI:10.1021/ja00207a038
