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Pd II ‐Catalyzed Enantioselective C(sp 3 )–H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group
Author(s) -
Xiao LiJun,
Hong Kai,
Luo Fan,
Hu Liang,
Ewing William R.,
Yeung KapSun,
Yu JinQuan
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202000532
Subject(s) - enantioselective synthesis , stereocenter , cyclobutane , chemistry , catalysis , ligand (biochemistry) , stereochemistry , combinatorial chemistry , substrate (aquarium) , medicinal chemistry , organic chemistry , ring (chemistry) , biology , ecology , biochemistry , receptor
Abstract 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 β‐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.