Enantioselective remote methylene C−H (hetero)arylation of cycloalkane carboxylic acids.

Stereoselective construction of g- and d-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 g-C−H (hetero)arylations of free cycloalkane carboxylic acids, which are essential carbocyclic building blocks in organic synthesis. The reaction establishes g-tertiary and a-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 d-C−H (hetero)arylation is also realized to establish d-stereocenters that are particularly challenging to access using classical methodologies. [ABSTRACT FROM AUTHOR]