Iridium-Catalyzed Intramolecular Asymmetric Allylic Dearomatization Reaction of Pyridines, Pyrazines, Quinolines, and Isoquinolines

The first Ir-catalyzed intramolecular
asymmetric allylic dearomatization
reaction of pyridines, pyrazines, quinolines, and isoquinolines has
been developed. Enabled by in situ formed chiral Ir-catalyst, the
dearomatized products were isolated in high levels of yield (up to
99% yield) and enantioselectivity (up to 99% ee). It is worth noting
that the Me-THQphos ligand is much more efficient than other tested
ligands for the dearomatization of pyrazines and certain quinolines.
Mechanistic studies of the dearomatization reaction were carried out,
and the results suggest the feasibility of an alternative process
which features the formation of a quinolinium as the key intermediate.
The mechanistic findings render this reaction a yet unknown type in
the chemistry of Reissert-type reactions. In addition, the utility
of this method was showcased by a large-scale reaction and formal
synthesis of (+)-gephyrotoxin.