page_title: Dynamic kinetic resolution in asymmetric synthesis
section_title: Enzyme-metal reactions
hierarchical_section_title: Dynamic kinetic resolution in asymmetric synthesis / Applications / Enzyme-metal reactions
caption_attribution_description: English: enzyne metal 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: More recently many research groups have tried to employ enzymes into DKR synthetic routes.  Due to the generally high specificity for substrates, enzymes prove to be vital catalysts for binding to only one stereoisomer in the racemic mixture.  In 2007 Bäckvall discovered an enzyme-metal coupled reaction that converts allylic acetates to allylic alcohols with excellent stereospecificity.
  In this reaction, a Pd(0) complex is used to interconvert the chirality of the acetate center at a rate fast enough to ensure complete racemization. When this is achieved the CALB enzyme selectively hydrolyzes the (R) substrate because of the low binding affinity for the (S) substrate. This gives almost exclusively the (R) allylic alcohol in 98% ee.
  To expand on this chemistry, Bäckvall designed a one-pot, two-reaction system that utilizes the stereochemical outcome of a DKR reaction to undergo a second energetically favorable reaction with high enantioselectivity.
  This time a ruthenium complex is used to racemize the allylic alcohol in much the same way as the previous example.  The addition of CALB catalyzes the reaction between the (R) isomer and the ester reagent to form a product with a diene and a dienophile.  This intermediate can then undergo a tandem Diels-Alder reaction to achieve a decent yield with 97% ee.
caption: Enzyme-metal coupled hydrolysis of acetates in stereoselective fashion.  Candida antarctica lipase B (CALB) is the catalytic enzyme used to select for the (R) acetate.
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