Pd^II -Catalyzed Enantioselective C(sp³ )-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group.

ABSTRACT: The use of chiral transient directing groups (TDGs) is a promising approach for developing Pd^II -catalyzed enantioselective C(sp³ )-H activation reactions. However, this strategy is challenging because the stereogenic center on the TDG is often far from the C-H bond, and both TDG covalently attached to the substrate and free TDG are capable of coordinating to Pd^II centers, which can result in a mixture of reactive complexes. We report a Pd^II -catalyzed enantioselective β-C(sp³ )-H arylation reaction of aliphatic ketones using a chiral TDG. A chiral trisubstituted cyclobutane was efficiently synthesized from a mono-substituted cyclobutane through sequential C-H arylation reactions, thus demonstrating the utility of this method for accessing structurally complex products from simple starting materials. The use of an electron-deficient pyridone ligand is crucial for the observed enantioselectivity. Interestingly, employing different silver salts can reverse the enantioselectivity.

SUBMITTER: Xiao LJ 

PROVIDER: S-EPMC7269848 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature