Asymmetric Two‐Component Alkenyl Catellani Reaction for the Construction of C—N Axial Chirality†

Abstract

Comprehensive SummaryHerein, we report an asymmetric two‐component alkenyl Catellani reaction for the construction of C—N axial chirality through a palladium/chiral norbornene cooperative catalysis and an axial‐to‐axial chirality transfer process. Various partially aromatic iodinated 2‐pyridones, quinolones, coumarin and uracil substrates react with 2,6‐disubstituted aryl bromides with a tethered amide group, to afford a wide variety of polycyclic C—N atropisomers (38 examples, up to 97% e.e.). The obtained C—N axial chirality originates from the preformed transient C—C axial chirality with high fidelity. The synthetic utility of this chemistry is demonstrated by facile preparation of complex quinoline and pyridine based C—N atropisomers through a N‐deprotection and aromatization sequence. In addition, a remote axial‐to‐central diastereoinduction process dictated by C—N axial chirality is observed with excellent diastereocontrol.