Asymmetric N-alkylation of Carbazoles by Cooperative Potassium-Hydrogen-Bond-Aryloxide Catalysis

The catalytic asymmetric N-alkylation of carbazoles to construct fully substituted stereocenters remains a significant challenge due to issues of regioselectivity, enantioselectivity, and steric hindrance. In this work, we address these obstacles by employing indol-2-ones as suitable electrophilic partners in a cooperative catalytic system. An in situ generated polyfunctional potassium catalyst, integrating Lewis acidic, Brønsted basic, and hydrogen-bond-donating sites, effectively promotes the nucleophilic amination process, exhibiting broad functional group tolerance and excellent selectivity. Mechanistic studies reveal that coordination of the carbonyl group in indol-2-ones to the potassium center is critical for lowering the activation barrier, while both the naphthalenolate and the naphthol moiety in the catalyst facilitate proton transfer. The resulting enantioenriched carbazole-oxindole hybrids, featuring two privileged scaffolds, may hold promising potential for medicinal chemistry applications.