PdII -Catalyzed Enantioselective C(sp3)-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group.Angew Chem Int Ed Engl. 2020 06 08; 59(24):9594-9600.AC
The use of chiral transient directing groups (TDGs) is a promising approach for developing PdII -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 PdII centers, which can result in a mixture of reactive complexes. We report a PdII -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.