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Updated: Jun 26, 2025

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Enantioselective remote methylene C-H (hetero)arylation of cycloalkane carboxylic acids
Tao Zhang1, Zi-Yu Zhang1, Guowei Kang1
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Abstract:
Stereoselective construction of γ- and δ-stereocenters in carbonyl compounds is a pivotal objective in asymmetric synthesis. Here, we report chiral bifunctional oxazoline-pyridone ligands that enable enantioselective palladium-catalyzed remote γ-C-H (hetero)arylations of free cycloalkane carboxylic acids, which are essential carbocyclic building blocks in organic synthesis. The reaction establishes γ-tertiary and α-quaternary stereocenters simultaneously in up to >99% enantiomeric excess, providing access to a wide range of cyclic chiral synthons and bioactive molecules. The sequential enantioselective editing of two methylene C-H bonds can be achieved by using chiral ligands with opposite configuration to construct carbocycles containing three chiral centers. Enantioselective remote δ-C-H (hetero)arylation is also realized to establish δ-stereocenters that are particularly challenging to access using classical methodologies.
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