Palladium-Catalyzed Enantioselective C-H Olefination to Access Planar-Chiral Cyclophanes by Dynamic Kinetic
Ziyang Dong1, Jia Li1, Ting Yao1
1Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875 (P. R., China.
Abstract:
Planar-chiral cyclophanes have received increasing attention for drug discovery and catalyst design. However, the catalytically asymmetric synthesis of planar-chiral cyclophanes has been a longstanding challenge. We describe the first Pd(II)-catalyzed enantioselective C-H olefination of prochiral cyclophanes. The low rotational barrier of less hindered benzene ring in the substrates allows the reaction to proceed through a dynamic kinetic resolution. This approach exhibits broad substrate scope, providing the planar-chiral cyclophanes in high yields (up to 99 %) with excellent enantioselectivities (up to >99 % ee). The ansa chain length scope studies reveal that the chirality of the cyclophanes arises from the bond rotation constraint of the benzene ring around the macrocycle plane, rather than the C-N axis. The C-H activation approach is also applicable to the late-stage modification of bioactive molecules and pharmaceuticals.
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