Cobalt‐Catalyzed Migratory <i>E</i> ‐Selective Asymmetric Aza‐Nozaki–Hiyama–Kishi Coupling

Abstract

ABSTRACT Transition‐metal–catalyzed migratory cross‐coupling offers an attractive strategy for converting readily available precursors into complex molecular architectures. However, current methods are typically restricted to a single migratory mode (e.g., chain‐walking, through‐space shift, or E/Z isomerization). Integrating multiple mechanistically distinct migratory events within a selective cross‐coupling manifold to unlock new chemical space and diverse isomeric products remains a formidable challenge. Herein, we report a cobalt‐catalyzed, migratory E ‐selective asymmetric aza‐NHK (Nozaki–Hiyama–Kishi) coupling of ortho ‐iodophenylethylenes with imines. The key to this process is a synergistic sequence that combines a through‐space 1,4‐Co/H shift with alkenylcobalt E/Z isomerization. Notably, mixtures of E/Z ‐alkenyl bromides are also viable substrates, undergoing an unprecedented alkenylcobalt E/Z isomerization prior to E ‐selective asymmetric coupling. This method provides efficient access to high‐value α‐chiral ( E )‐allylic amines with exceptional control over regio‐, E/Z ‐, and enantioselectivity.