Synthesis of α-Trifluoromethyl Esters

  • Author:
  • Published: 15 June 2018
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
  • Source / Publisher: Organic Letters/ACS Publications
  • Associated Societies: American Chemical Society (ACS), USA
thumbnail image: Synthesis of α-Trifluoromethyl Esters

Organic compounds with fluorine substituents can be very useful, e.g., in pharmaceutical chemistry. One commonly used fluorinated group is CF3. Reactions that allow the connection of this group to sp3-hybridized carbon atoms are rare, and especially the α-trifluoromethylation of carbonyl derivatives is still challenging.

Thomas Poisson, Normandy University, Rouen, France, and Institut Universitaire de France, Paris, Tatiana Besset, Normandy University, and colleagues have developed a synthesis that provides easy access to α-trifluoromethyl esters (pictured) and starts from readily available α-chloro aldehydes. The team used an N-Heterocyclic carbene (NHC) organocatalyst, Togni's reagent (3,3-dimethyl-1-(trifluoromethyl)-1,2-benziodoxole) as a CF3+ source, and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) as a base in a mixture of methanol and dichloromethane at 0 °C.

The desired α-trifluoromethyl esters were obtained in moderate to good yields. The proposed reaction mechanism involves an addition of the NHC catalyst to the carbonyl group of the α-chloro aldehyde, an abstraction of HCl by the base to form an enolate, an electrophilic attack of the CF3+ source at the α-position, and the formation of the ester regeneration of the catalyst via a nucleophilic attack by methanol.


Article Views: 4253

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

If you would like to reuse any content, in print or online, from, please contact us first for permission and consult our permission guidance prior to making your request

Follow on Facebook Follow on Twitter Follow on YouTube Follow on LinkedIn Follow on Instagram RSS Sign up for newsletters

Magazine of Chemistry Europe (16 European Chemical Societies) published by Wiley-VCH