Enantioselective Synthesis of Biaryl Atropisomers by Pd‐Catalyzed C−H Olefination using Chiral Spiro Phosphoric Acid Ligands

• Published in: Angewandte Chemie International Edition 2019-05, Vol.58 (20), p.6708-6712
• Main Authors: Luo, Jun, Zhang, Tao, Wang, Lei, Liao, Gang, Yao, Qi‐Jun, Wu, Yong‐Jie, Zhan, Bei‐Bei, Lan, Yu, Lin, Xu‐Feng, Shi, Bing‐Feng
• Format: Article
• Language: English
• Subjects: atroposelectivity; Chemical synthesis; chiral spiro phosphoric acids; C−H olefination; Density functional theory; Enantiomers; Ligands; Palladium; Phosphoric acid; Quinoline; quinoline biaryls; Stereoselectivity
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201902126

The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, we reported the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination. A novel chiral spiro phosphoric acid, STRIP, was identified as a superior ligand for this transformation. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee). Density functional theory was used to gain a theoretical understanding of the enantioselectivities in this reaction. The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination is reported. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee).