Asymmetric Remote meta-C-H Activation Controlled by a Chiral Ligand

The use of a chiral ligand for stereocontrol has assisted the development of a number of asymmetric functionalization of proximal C-H bonds. Herein, we report a chiral ligand-controlled, asymmetric remote meta-C-H activation of arenes, leading to asymmetric C-H olefination and arylation of hydrocinnamic acid derivatives through desymmetrization with Ac-L-Phe-OH as the chiral ligand using a Pd(II) catalyst. The origins of the enantioselectivity were explained with density functional theory calculations. The larger distortion energy of the substrate part in the C-H bond activation transition structure S-TS1 is the major controlling factor that disfavors the formation of the S-enantiomer product.

Automated summary

The use of a chiral ligand-controlled, asymmetric remote meta-C-H activation enables asymmetric C-H olefination and arylation of hydrocinnamic acid derivatives. The origins of the enantioselectivity were explained using density functional theory calculations.