Atroposelective Synthesis of Conjugated Diene-Based Axially Chiral Styrenes via Pd(II)-Catalyzed Thioether-Directed Alkenyl C-H Olefination

The efficient stereoselective synthesis of conjugated dienes, especially those with axial chirality, remains a great challenge. Herein, we report the highly atroposelective synthesis of axially chiral styrenes with a conjugated 1,3-diene scaffold via a Pd(II)-catalyzed thioether-directed alkenyl C-H olefination strategy. This strategy features easy operation, mild reaction conditions, high functional group tolerance (69 examples), complete Z-selectivity, and excellent enantioselectivities (up to 99% ee). Notably, the highly enantioselective synthesis of atropisomers with two stereogenic axes were also achieved using this strategy (up to 99% ee and 97:3 dr). Moreover, the reaction could be scaled up, and the resulting axially chiral styrenes could be easily oxidized into chiral sulfoxide derivatives with high diastereoselectivities, which showed great promise as a new type of sulfur-olefin ligand.

Automated summary

Efficient synthesis of axially chiral styrenes with high enantioselectivity was achieved using a Pd(II)-catalyzed thioether-directed alkenyl C-H olefination strategy. The reaction showed ease of operation, mild conditions, high functional group tolerance, complete Z-selectivity, and excellent enantioselectivities, with potential for scaling up and further derivatization into chiral sulfoxide ligands.