First One Step Regioselective Acylation

  • Author: Li Grundl
  • Published: 05 August 2018
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
  • Source / Publisher: Journal of the American Chemical Society/ACS Publications
  • Associated Societies: American Chemical Society (ACS), USA
thumbnail image: First One Step Regioselective Acylation

The Friedel-Crafts acylation, an electrophilic aromatic substitution with electronic-controlled regioselectivity, is a commonly used method to synthesize aryl ketones. Although regioselective arene acylation using other approaches is possible, it usually requires multiple steps and precious-metal catalysts.

Christopher J. Douglas and colleagues, University of Minnesota—Twin Cities, Minneapolis, USA, have developed a new method for the sterically controlled regioselective acylation of arenes and heteroarenes (example product pictured). The team used phenyl salicylates as the acylation reagents, [Ir(cod)OMe]2 (cod = 1,5-cyclooctadiene) as a catalyst, and rac-2-(di-tert-butylphosphino)-1,1'-binaphthyl as a ligand. The reactions were performed in the respective arenes or heteroarenes, which were used in solvent quantities, at 170 °C.

The reaction tolerates a broad range of functional groups on the salicylate ester. Simple electron-rich arenes as substrates react particularly well under the conditions. The researchers suggest that the sterically controlled acylation is achieved via a concerted metalation–deprotonation C–H activation. The developed reaction offers substitution patterns previously inaccessible in a single step. The method's usefulness was demonstrated by a concise synthesis of the anticancer agent hydroxyphenstatin.


Article Views: 1104

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, please contact us first for permission. more

CONNECT: on Facebook on Twitter on YouTube on LinkedIn Sign up for our free newsletter

A product of ChemPubSoc Europe (16 European Chemical Societies)and Wiley-VCH