Pd(II)-Catalyzed enantioselective arylation of unbiased methylene C(sp3)-H bonds enabled by a 3,3'-F2-BINOL ligand

Xu Yang; Meng-Xue Jiang; Tao Zhou; Ye-Qiang Han; Xue-Tao Xu; Kun Zhang; Bing-Feng Shi

doi:10.1039/d1cc01690c

Pd(II)-Catalyzed enantioselective arylation of unbiased methylene C(sp³)-H bonds enabled by a 3,3'-F₂-BINOL ligand

Chem Commun (Camb). 2021 Jun 3;57(45):5562-5565. doi: 10.1039/d1cc01690c.

Authors

Xu Yang¹, Meng-Xue Jiang¹, Tao Zhou², Ye-Qiang Han², Xue-Tao Xu¹, Kun Zhang¹, Bing-Feng Shi³

Affiliations

¹ School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, China.
² Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310027, China. hugh10021993@zju.edu.cn bfshi@zju.edu.cn.
³ Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310027, China. hugh10021993@zju.edu.cn bfshi@zju.edu.cn and College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, China.

PMID: 33969855
DOI: 10.1039/d1cc01690c

Abstract

Palladium-catalyzed asymmetric functionalization of unbiased methylene C(sp3)-H bonds is a long-standing challenge. Here, we report a Pd(ii)-catalyzed highly enantioselective arylation of unbiased methylene C(sp3)-H bonds enabled by a strongly coordinating bidentate 2-pyridinylisopropyl (PIP) directing group and an easily accessible 3,3'-F2-BINOL chiral ligand. The use of aryl iodides with the combination of 3,3'-F2-BINOL was beneficial for high enantiocontrol. A range of aliphatic amides and aryl iodides were tolerated, providing the desired arylated products in high enantioselectivities (up to 96% ee). The PIP directing group could be removed under mild conditions without erosion of enantiopurity.