Organocatalytic Atroposelective Aldol Condensation: Synthesis of Axially Chiral Biaryls by Arene Formation

Axially chiral compounds are of significant importance in modern synthetic chemistry and particularly valuable in drug discovery and development. Nonetheless, current approaches for the preparation of pure atropisomers often prove tedious. We demonstrate here a synthetic method that efficiently transfers the stereochemical information of a secondary amine organocatalyst into the axial chirality of tri‐ortho‐substituted biaryls. An aromatic ring is formed during the dehydration step of the described aldol condensation cascade, leading to highly enantioenriched binaphthyl derivatives. The fundamental course of the reaction is related to the biosynthesis of aromatic polyketides. Head‐turning! An organocatalytic atroposelective aldol condensation to tri‐ortho‐substituted biaryls is described. Key to the process is an efficient transfer of the stereochemical information of a secondary amine catalyst into the axis of chirality of binaphthyl products. The reaction proceeds analogous to the aromatic polyketide biosynthesis and is distinct in its initiation by virtue of dienamine formation. This method allows for the synthesis of axially chiral biaryls with remarkable atroposelectivity of up to e.r. 99:1.