Rh(III)-Catalyzed Regioselective C8-Alkylation of Quinoline N-Oxides with Maleimides and Acrylates

Herein, we disclose the Rh(III)-catalyzed selective C8-alkylation of quinoline N-oxides with maleimides and acrylates. The main features of the reaction include complete C8-selectivity and broad substrate scope with good to excellent yields. The reaction also proceeded well with unprotected maleimide. The applicability of the developed methodology is demonstrated with gram-scale synthesis and post-modification of the alkylated product. Preliminary mechanistic study revealed that the reaction proceeds through a five-membered rhodacycle and involves proto-demetalation step.

Automated summary

This research presents a Rh(III)-catalyzed selective C8-alkylation of quinoline N-oxides with maleimides and acrylates, showing good selectivity and substrate scope. The methodology was also demonstrated to be applicable for gram-scale synthesis and post-modification.