Nonenzymatic Dynamic Kinetic Resolution of Secondary Alcohols via Enantioselective Acylation: Synthetic and Mechanistic Studies

Sarah Yunmi Lee, Jaclyn M. Murphy, Atsushi Ukai, and Gregory C. Fu
J. Am. Chem. Soc
DOI:10.1021/ja307425g

Fu1

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).

Fu2

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.

Fu3

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.

Advertisements

3 thoughts on “Nonenzymatic Dynamic Kinetic Resolution of Secondary Alcohols via Enantioselective Acylation: Synthetic and Mechanistic Studies

  1. mikey

    Fantastic entry! Though I think your explanation of how the ruthenium catalyst works is snot quite right. After reading the paper, I think that the Ru catalyst acts as a racemization catalyst of secondary alcohols, rather than a deacylation catalyst. The planar chiral Fe catalyst acylates one enantiomer of alcohol preferentially and the Ru catalyst racemizes the remaining enriched alcohol so that all of the alcohol is funneled into one enantiomer. Fu shows an experiment in the paper where Ru racemizes the alcohol even without any carbonate in solution.

    Reply
  2. georgek86 Post author

    @mikey:

    I think you are right. Sorry about any confusion. After having another read through the paper it seems that I got them a bit mixed up. Cheers for spotting that.

    Reply

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s