Photoinduced Copper‐Catalyzed Stereoselective C(sp <sup>3</sup> )‐H Amination Enabled by Preorganized Multiple Noncovalent Interactions
Abstract
ABSTRACT Chiral α ‐amino cyclic amines are essential bioactive molecular skeletons that play a crucial role in regulating the biological functions of diverse molecules. Despite their significance, the asymmetric C─H amination of saturated cyclic amines using readily available nitrogen sources has not been accomplished. In this work, a photoinduced copper‐catalyzed highly enantioselective α ‐C(sp 3 )‐H amination of cyclic amines with pharmaceutically valuable aromatic and α , β ‐unsaturated amides is developed. In addition to amides, diverse aromatic N ‐heterocycles, as well as the unstable and challenging imine, can also participate in the reaction, delivering various functionalized α ‐amino cyclic amines with high diastereoselectivity. Mechanistic study and DFT calculation indicate that the C─N bond is formed through the radical addition of α ‐amino radical to Cu(II)‐amide species followed by the inner‐sphere reductive elimination. The preassembly of ( R )‐BINOL with the BOPA‐copper(II) benzamide via hydrogen bonding and CH···π interactions can enhance the stereoselectivity through exclusive π···π stacking interaction in ( R )‐pathway. The unique reaction model featuring photoredox transition‐metal catalysis, radical cross‐coupling, and multiple noncovalent interactions is the key to success of this chemistry.
Article Details
Authors (13)
Sijia Li
Cuihuan Geng
State Key Laboratory of Power Grid Environmental Protection, College of Chemistry and Molecular Sciences
Xiaoli Zhao
Chenwei Wang
State Key Laboratory of Green Pesticide, Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei 430079, P. R. China
Kaiyao Yuan
State Key Laboratory of Green Pesticide Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction Ministry of Education College of Chemistry Central China Normal University (CCNU) Wuhan Hubei P. R. China
He Zhang
Jialian Zheng
CCNU-uOttawa Joint Research Centre, State Key Laboratory of Green Pesticide, Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei 430079, P. R. China
Mengxiao Jiang
State Key Laboratory of Green Pesticide Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction Ministry of Education College of Chemistry Central China Normal University (CCNU) Wuhan Hubei P. R. China
Guohao Cui
State Key Laboratory of Green Pesticide Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction Ministry of Education College of Chemistry Central China Normal University (CCNU) Wuhan Hubei P. R. China
Wenhan Xu
Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan 430079, P. R. China
Xiaotian Qi
State Key Laboratory of Power Grid Environmental Protection, College of Chemistry and Molecular Sciences
Guozhu Zhang
State Key Laboratory of Green Pesticide, Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University (CCNU), 152 Luoyu Road, Wuhan, Hubei 430079, P. R. China
Rui Guo