Rhodium-Catalyzed Atroposelective C–H Alkylation of 1-Aryl Isoquinoline Derivatives with Cyclopropanols

Highly efficient synthesis of axially chiral biaryls bearing a β-aryl ketone framework is achieved by an atroposelective C–H alkylation reaction of 1-aryl isoquinoline derivatives with cyclopropanols. Judiciously choosing SPINOL-derived trisubstituted SCpRh as the catalyst is crucial for the desired asymmetric alkylation reaction over the competitive formation of alkenylation byproducts, delivering the target axially chiral biaryls in 40–99% yields and 48–97% ee. Further mechanistic studies suggested that Rh-catalyzed C–H bond cleavage serves as the turnover-limiting step, while the Cu-mediated transformation of cyclopropyl alcohols into their corresponding enones is established as the key source of the active alkylation reagents.