Cp*Ir(III)-Catalyzed Asymmetric Tandem Intramolecular Aziridination/Aza-Semipinacol Rearrangement of Alkenyl 1,4,2-Dioxazol-5-one

Aza-semipinacol
rearrangement provides facile access to the quaternary
carbon center adjacent to imine or enamine. Despite the enormous advances
that have been witnessed during the last two decades, the catalytic
asymmetric aza-semipinacol has been far less explored. In this study,
we disclose an innovative [Cp*IrCl2]2-catalyzed
tandem aziridination/aza-semipinacol rearrangement of alkenyl 1,4,2-dioxazol-5-one,
facilitating the synthesis of cyclopenta[b]pyridin-2-ones
with a quaternary carbon center. Furthermore, we successfully achieved
Cp*Ir(III)-catalyzed asymmetric tandem aziridination/aza-semipinacol
rearrangement of alkenyl 1,4,2-dioxazol-5-one, using 2,4,6-trimethylphenylacyl
tailored chiral 2-(aminomethyl)pyridine as the ligand. By taking advantage
of this novel chiral catalyst, bicyclic lactams were obtained with
good to excellent enantioselectivities via a catalytic asymmetric
cascade. Density functional theory (DFT) calculations suggest that
the reaction is initiated with the generation of an Ir-acyl nitrenoid,
which undergoes enantioselective intramolecular aziridination under
the influence of the chiral ligand. The ensuing aza-semipinacol rearrangement
driven by the release of ring strain leads to enantioenriched bicyclic
lactams via a stereospecific rearrangement.