Synthesis of Axially Chiral Styrenes through Pd-Catalyzed Asymmetric C-H Olefination Enabled by an Amino Amide Transient Directing Group

Abstract

The atroposelective synthesis of axially chiral styrenes remains a formidable challenge due to their relatively lower rotational barriers compared to the biaryl atropoisomers. Herein, we describe the construction of axially chiral styrenes through Pd^II -catalyzed atroposelective C-H olefination, using a bulky amino amide as a transient chiral auxiliary. Various axially chiral styrenes were produced with good yields and high enantioselectivity (up to 95 % yield and 99 % ee). Carboxylic acid derivatives of the resulting axially chiral styrenes showed superior enantiocontrol over the biaryl counterparts in Co^III -catalyzed enantioselective C(sp³ )-H amidation of thioamide. Mechanistic studies suggest that C-H cleavage is the enantioselectivity-determining step.

Keywords: C−H olefination; atroposelectivity; axially chiral styrenes; palladium; transient directing groups.