Enantioselective Synthesis of Axially Chiral Tetrasubstituted Alkenes by Copper‐Catalyzed C(sp2)–H Functionalization of Arenes with Vinyl Cations

• Published in: Angewandte Chemie International Edition Vol. 64; no. 6; pp. e202418254 - n/a
• Main Authors: Weng, Chen‐Yong, Liu, Li‐Gao, Sun, Miao, Lu, Xin, Hong, Xin, Ye, Long‐Wu, Zhou, Bo
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 03.02.2025
• Edition: International ed. in English
• Subjects: Alkenes; Alkynes; Aromatic compounds; Asymmetric Catalysis; Asymmetric synthesis; Asymmetry; Axially Chiral Alkenes; C(sp2)-H Functionalization; Catalysis; Cations; Chemical synthesis; Copper; Enantiomers; Intermediates; Reaction mechanisms; Regioselectivity; Styrenes; Vinyl Cations; Asymmetric Catalysis; Vinyl Cations; Axially Chiral Alkenes; C(sp2)-H Functionalization; Alkynes
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202418254

Axially chiral tetrasubstituted alkenes are of increasing value and interest in chemistry‐related areas. However, their catalytic asymmetric synthesis remains elusive, owing to the high steric repulsion and relatively low conformational stability. Herein, we disclose the straightforward construction of atropisomeric tetrasubstituted alkenes by effective enantiocontrol in a reaction with vinyl cation intermediates. This copper‐catalyzed enantioselective C(sp2)‐H functionalization of sterically hindered (hetero)arenes with vinyl cations enables the efficient and atom‐economical preparation of axially chiral acyclic tetrasubstituted styrenes and pyrrolyl ethylenes with high atroposelectivities. Importantly, this reaction represents the first example of the assembly of axially chiral alkenes via vinyl cations. Computational mechanistic studies reveal the reaction mechanism, origin of regioselectivity, Z/E selectivity and enantioselectivity. The synthetic utility has been demonstrated by diverse product derivatizations, chiral organocatalyst synthesis, as well as further applications in asymmetric catalysis. A copper‐catalyzed enantioselective C(sp2)‐H functionalization of arenes with vinyl cations has been realized, enabling the atom‐economical preparation of axially chiral acyclic tetrasubstituted alkenes. This transformation is the first example of the assembly of atropisomeric alkenes via vinyl cations. Notably, the constructed axially chiral skeletons were shown to be applicable to asymmetric catalysis.