<i>ortho</i> ‐C─H Alkylation of Aryl Chlorides by a Catellani Strategy

J Jian‐Shu Wang (Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China) Z Zequan Liu G Guangyin Qian (Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China) X Xiahe Chen L Liming Cao T Tiaozhen Yu (Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China) J Jinxiang Ye (State Key Laboratory of Metabolism and Regulation in Complex Organisms, Hubei Research Center of Fundamental Science-Chemistry, Engineering Research Center of Organosilicon Compounds and Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric OptoElectronic Materials, College of Chemistry and Molecular Sciences, the Institute for Advanced Studies, Taikang Center for Life and Medical Sciences, School of Artificial Intelligence) Y Yuanyuan Ma (Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, School of Medicine) S Shuqing Chen (Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology) Z Zuo Yang (Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China) H Hong‐Gang Cheng (Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China) Y Yun‐Fang Yang (Center for Phosphorescent Material Research State Key Laboratory of Green Chemical Synthesis and Conversion College of Chemical Engineering Zhejiang University of Technology Hangzhou Zhejiang 310014 P.R. China) Q Qianghui Zhou (State Key Laboratory of Metabolism and Regulation in Complex Organisms, Hubei Research Center of Fundamental Science-Chemistry, Engineering Research Center of Organosilicon Compounds and Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric OptoElectronic Materials, College of Chemistry and Molecular Sciences, the Institute for Advanced Studies, Taikang Center for Life and Medical Sciences, School of Artificial Intelligence)

Abstract

Abstract Herein we report a general and practical palladium/norbornene catalysis system that effectively promotes difunctionalization of less reactive aryl chlorides. The key to success lies in the use of a particular norbornene (NBE) derivative as a powerful mediator that synergistically cooperates with the palladium catalyst and an electron‐rich phosphine ligand. A broad spectrum of electronically diverse aryl chlorides (57 examples) delivered the corresponding ortho ‐C─H alkylation/ ipso ‐olefination products in moderate to good yields. Notably, this protocol features excellent functional‐group tolerance, high concentration, scalability, and late‐stage functionalization of complex aryl chlorides. Furthermore, by integrating this chemistry with its counterparts involving aryl iodides and bromides, an intriguing triple‐Catellani reaction sequence was developed, rapidly increasing molecular complexity and diversity. Finally, DFT calculations were performed, revealing that noncovalent C─H⋯O interactions between the XPhos ligand and the NBE mediator promote the pivotal NBE insertion step.

Article Details

Volume / Issue Vol. 64, Issue 31
Published July 28, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (13)

J

Jian‐Shu Wang

Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China

Z

Zequan Liu

G

Guangyin Qian

Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China

X

Xiahe Chen

L

Liming Cao

T

Tiaozhen Yu

Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China

J

Jinxiang Ye

State Key Laboratory of Metabolism and Regulation in Complex Organisms, Hubei Research Center of Fundamental Science-Chemistry, Engineering Research Center of Organosilicon Compounds and Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric OptoElectronic Materials, College of Chemistry and Molecular Sciences, the Institute for Advanced Studies, Taikang Center for Life and Medical Sciences, School of Artificial Intelligence

Y

Yuanyuan Ma

Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, School of Medicine

S

Shuqing Chen

Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology

Z

Zuo Yang

Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China

H

Hong‐Gang Cheng

Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Engineering Research Center of Organosilicon Compounds &amp; Materials (Ministry of Education) Hubei Key Lab on Organic and Polymeric OptoElectronic Materials College of Chemistry and Molecular Sciences The Institute for Advanced Studies and TaiKang Center for Life and Medical Sciences Wuhan University Wuhan 430072 China

Y

Yun‐Fang Yang

Center for Phosphorescent Material Research State Key Laboratory of Green Chemical Synthesis and Conversion College of Chemical Engineering Zhejiang University of Technology Hangzhou Zhejiang 310014 P.R. China

Q

Qianghui Zhou

State Key Laboratory of Metabolism and Regulation in Complex Organisms, Hubei Research Center of Fundamental Science-Chemistry, Engineering Research Center of Organosilicon Compounds and Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric OptoElectronic Materials, College of Chemistry and Molecular Sciences, the Institute for Advanced Studies, Taikang Center for Life and Medical Sciences, School of Artificial Intelligence