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.