γ-C(sp3)–H Activation of Ketones

  • Author: Li Grundl
  • Published: 18 March 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: γ-C(sp<sup>3</sup>)–H Activation of Ketones

The transition-metal-catalyzed β-C(sp3)–H functionalization of carbonyl compounds has been well developed. However, only few examples of γ-C(sp3)–H activation are known and these reactions are limited to substrates containing a β-quaternary carbon center. γ-C(sp3)–H activations do not happen easily because the reaction needs to go through a thermodynamically less favored six-membered metallacycle.


Jin-Quan Yu, The Scripps Research Institute, La Jolla, CA, USA, and colleagues have developed the first Pd(OAc)2-catalyzed γ-C(sp3)–H (hetero)arylation of ketones without a β-quaternary carbon center. The key to this reaction is using an auxiliary, 2,2-dimethyl aminooxyacetic acid, as a directing group and 5-nitro-2-pyridone as a ligand. The reactions of ketones with the directing group and (hetero)aryl iodides are carried out in hexafluoroisopropanol at 120 °C in the presence of CF3COOAg. The directing group can be removed by an Mn(II)-catalyzed reaction.


The researchers have isolated and characterized a rare PPh3-stabilized six-membered palladacycle intermediate during their study of the reaction mechanism. The utility of the synthesis method has been demonstrated by a sequential β- and γ-C(sp3)–H (hetero)arylation of muscone.


 

Article Views: 755

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


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