Catalytic Atroposelective aza-Grob Fragmentation: Unlocking a New Strategy for Axially Chiral Biarylnitriles

Abstract We report on the development of a catalytic atroposelective aza-Grob fragmentation of α-keto oxime esters—the first of its kind catalytic asymmetric version of this classical reaction. By leveraging torsional strain and multiple hydrogen-bonding activation, a catalytic asymmetric addition, followed by a stereospecific carbon–carbon cleavage reaction was developed, delivering axially chiral biarylnitriles in high yield and enantioselectivity. In this Synpact article, we present the conceptual framework of the catalytic asymmetric aza-Grob fragmentation and highlight the key structural features that enable atroposelective C–C bond scission.