page_title: Dynamic kinetic resolution in asymmetric synthesis
section_title: Asymmetric aldol reaction
hierarchical_section_title: Dynamic kinetic resolution in asymmetric synthesis / Applications / Asymmetric aldol reaction
caption_attribution_description: English: felkin model for aldol reaction
context_page_description: Dynamic kinetic resolution in chemistry is a type of kinetic resolution where 100% of a racemic compound can be converted into an enantiopure compound. It is applied in asymmetric synthesis. Asymmetric synthesis has become a much explored field due to the challenge of creating a compound with a single 3D structure. Even more challenging is the ability to take a racemic mixture and have only one chiral product left after a reaction. One method that has become an exceedingly useful tool is dynamic kinetic resolution. DKR utilizes a center of a particular molecule that can be easily epimerized so that the and enantiomers can interconvert throughout the reaction process. At this point the catalyst can selectively lower the transition state energy of a single enantiomer, leading to almost 100% yield of one reaction pathway over the other. The figure below is an example of an energy diagram for a compound with an and isomer.
  If a catalyst is able to increase ΔΔG≠ to a sufficient degree, then one pathway will dominate over the other, leading to a single chiral product. Manipulating kinetics therefore becomes a powerful way to achieve asymmetric products from racemic starting materials.
context_section_description: In addition to hydrogenation reactions, other bonds have been formed using DKR and are highly successful.  The aldol reaction has been extensively researched primarily because of the inherent challenge of forming a carbon-carbon bond.  Ward and colleagues have been able to use the proline-catalyzed aldol reaction in tandem with dynamic kinetic resolution to obtain a high enantioselective reaction.
  In this reaction proline catalyzes the reaction through creation of an enamine intermediate that is highly nucleophilic. The acid group on the catalyst helps facilitate the carbon-carbon bond formation by coordinating with the aldehyde oxygen.  This greatly improves stereoselectivity and yield.  Ward and his associates also found that by adding trace amounts of water to the DMSO solvent, it greatly increase the yield of the reaction, most likely by aiding proton transfer from proline to the newly forming alcohol.
  The selectivity for this product can best be explained by the Felkin model.  The cyclic (E)-enamine is able to undergo a favorable transition state where the aldehyde adopts an anti relationship relative to the incoming nucleophile, as well as a 1,2 syn relationship between the aldehyde and its adjacent ring system.  The transition state is shown above.
caption: Felkin Model of the transition state.  The stereochemistry is determined by the directing hydrogen bond and increased distance between the bulky sulfur rings.
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