biostudies-literature00380Xiao LJNIGMS NIH HHS9594-9600https://www.ebi.ac.uk/biostudies/studies/S-EPMC7269848biostudies-literatureUnknown59(24)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.Angewandte Chemie (International ed. in English)Pd^II -Catalyzed Enantioselective C(sp³ )-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group.PMC7269848R01 GM084019Yu JQXiao LJYeung KSHong KLuo FHu LEwing WR38falsePd^II -Catalyzed Enantioselective C(sp³ )-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group.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.2020-01-01T00:00:00Z2020 Jun2022-02-10T13:55:20.692Z2022-02-10T13:55:20.692ZS-EPMC72698483215531310.1002/anie.202000532