Enantioselective 3-Fluorochromane Synthesis

  • Author: Angewandte Chemie International Edition
  • Published Date: 22 July 2020
  • Source / Publisher: Angewandte Chemie International Edition/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
thumbnail image: Enantioselective 3-Fluorochromane Synthesis

Changing the physicochemical properties of small molecules by fluorination is a useful strategy in drug discovery. Often, motifs that are commonly found in nature can be tuned for pharmaceutical applications by the strategic introduction of fluorine. The heterocycle chromane is found in numerous biologically active molecules, however, methods to access 3-fluorochromanes (pictured above) are rare.


Ryan Gilmour and colleagues, University of Münster, Germany, have developed a iodine-catalysis-based approach to convert allyl phenyl ethers into enantioenriched 3-fluorochromanes (pictured below). The team used a chiral, C2-symmetric iodoresorcinol-based catalyst, Selectfluor® as an oxidant, and amine/HF mixtures as reactants to create a variety of fluorinated chromanes in an enantioselective fashion.


A Selectfluor®‐mediated oxidation converts the catalyst to a hypervalent ArIF2 species in situ (pictured below). This species then enables the fluorocyclization of the substrate. The overall process is stereospecific with enantiomeric ratios up to 93:7 and allows rapid access to biologically relevant 3-fluorochromanes.

 


 

 

Article Views: 596

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

Bookmark and Share

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission. more


CONNECT:

ChemistryViews.org on Facebook

ChemistryViews.org on Twitter ChemistryViews.org on YouTube ChemistryViews.org on LinkedIn Sign up for our free newsletter


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