Sarah Yunmi Lee, Jaclyn M. Murphy, Atsushi Ukai, and Gregory C. Fu
J. Am. Chem. Soc
Dynamic Kinetic Resolution is a well established methodology for the stereoselective preparation of chemicals, which overcomes the low yield issue inherent in classic kinetic resolution. There are two strategies; the first one relies on the fast interconvertion of the two enantiomers of the starting material between them and the difference in relative conversion rates to the desired product (A). The second relies on the conversion of only one of the enantiomers of the product back to the starting material (B).
Although the first strategy can be implemented without the need of an enzyme, the second required atleast one enzyme – usually a deacetylase enzyme – to be successfully applied. Only recently, a non-enzymatic dynamic kinetic resolution methodology for the acylation of secondary amines, relying on the second approach has been reported. A ferrocene is used for the acylation of the substrate, whilst a ruthenium complex deacetylates only one enantiomers of the acylated product. The authors demonstrated the applicability of their method on a variety of substrates.
This non-enzymatic method is not fascinating only because the lack of an enzyme which can prove to be scare or even not compatible with the reaction conditions. It overcomes the “other enantiomer” issue. Enzymes are fantastic catalysts however they are evolved specifically to do one job and one job only, making them inherently useless for the preparation of the other enantiomer of the desired product. For non-enzymatic processes such as the one above this is not an issue. If the enantiomer of the ruthenium catalyst was used then the product obtained would have the opposite stereochemistry.
This is the first non-enzymatic dynamic kinetic resolution method for secondary alcohols reported and hopefully it will provide incentive for future development as well as inspiration for more such approaches.