Pd-II-Catalyzed Enantioselective C(sp(3))-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group

• Published in: Angewandte Chemie International Edition Vol. 59; no. 24; pp. 9594 - 9600
• Main Authors: Xiao, Li-Jun, Hong, Kai, Luo, Fan, Hu, Liang, Ewing, William R., Yeung, Kap-Sun, Yu, Jin-Quan
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 08.06.2020
• Subjects: Benzene - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; Cyclobutanes - chemistry; Electron Transport; Ketones - chemistry; Palladium - chemistry; Physical Sciences; Science & Technology; Stereoisomerism; ACTIVATION; INDOLINES; ALDEHYDES; arylation; DESYMMETRIZATION; FUNCTIONALIZATION; transient directing groups; C-H activation; C-H ARYLATION; AMINES; BONDS; CONSTRUCTION; pyridone ligands; palladium; C(SP)-H; C−H activation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202000532

The use of chiral transient directing groups (TDGs) is a promising approach for developing Pd-II-catalyzed enantioselective C(sp(3))-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 beta-C(sp(3))-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.