Asymmetric Two-Component Alkenyl Catellani Reaction for the Construction of C-N Axial Chirality

Herein, 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.