Simultaneous construction of axial and planar chirality by gold/TY-Phos-catalyzed asymmetric hydroarylation

Abstract

The simultaneous construction of two different chiralities via a simple operation poses considerable challenge. Herein a cationic gold-catalyzed asymmetric hydroarylation of ortho-alkynylaryl ferrocenes derivatives is developed, which enable the simultaneous construction of axial and planar chirality. The here identified TY-Phos derived gold complex is responsible for the high yield, good diastereoselectivity (>20:1 dr), high enantioselectivities (up to 99% ee) and mild conditions. The catalyst system also shows potential application in the synthesis of chiral biaryl compounds. The cause of high enantioselectivity of this hydroarylation is investigated with density functional theory caculation.

PC-Phos Enabled Catalytic Palladium-heteroallyl Asymmetric Cycloaddition

“…Other screened ligands resulted in varying degrees of isomerization of Z - 2a , which is responsible for the lower yield of the cycloaddition product. Inspired by the previous findings that tuning the electron nature of the backbone could affect the catalytic activity and enantioselectivity, , a new PC-Phos ( PC5 ) was then designed by introducing the di- tert -butyl group on the xanthene backbone. To our delight, the yield was indeed significantly improved from 80% to 98% with the enantioselectivity increased from 97% to 99% ee.…”

Ir-Catalyzed Asymmetric Hydroarylation of Alkynes for the Synthesis of Axially Chiral Heterobiaryls

“…Among the latter approaches, ortho -directed alkenylation of functionalized arenes via alkyne hydroarylation has been broadly explored because of the excellent levels of regio- and stereocontrol ( syn ) reached with a wide range of heteroatom-based directing groups and different metal-based catalysts . Despite the progress made in this field, however, most of the alkyne hydroarylation reactions reported for the asymmetric synthesis of axially, helically, or planar chiral compounds are nondirected intramolecular Friedel–Crafts-type alkenylations that proceed via the formation of metal π-alkyne complexes (Scheme B). Compared with the better-established methodologies for the asymmetric hydroarylation of vinyl ethers, 1,3-dienes, alkenes, or bicycloalkenes, the hydroarylation of alkynes represents a more challenging problem, particularly in controlling regioselectivity.…”

Enantioselective Assembly of Ferrocenes with Axial and Planar Chiralities via Palladium/Chiral Norbornene Cooperative Catalysis

“…Therefore, the development of novel strategies for the quick assembly of ferrocenes with both axial and planar chiralities from readily available starting materials is a highly desirable yet challenging subject. 17 Recently, the research on simultaneous construction of multiple chiralities has been flourishing. 19−27 For instance, in 2022, Shi and co-workers reported a one-step construction of atropisomers with vicinal C−C and C−N chiral diaxes by cobalt-catalyzed intramolecular atroposelective C−H annulation.…”