Ru(ii)-catalyzed site-selective N-directed C(sp2)–H alkylation of quinoxalinones with maleimide

Abstract

An efficient and highly regioselective ruthenium(II)-catalyzed ortho-C–H alkylation of N-alkyl-3-phenylquinoxalin-2(1H)-ones with a broad array of N-alkyl maleimides is described. Systematic optimization identified [Ru(p-cymene)Cl₂]₂/AgSbF₆/AcOH/Cu(OAc)₂·H₂O as an effective catalytic system, operating in 1,2-dichloroethane at 120 °C under N₂ to furnish ortho-alkylated products in yields up to 88%. The reaction shows remarkable tolerance toward both electron-donating and electron-withdrawing substituents on the quinoxalinone arene, diverse modifications on the heterocyclic core, and a wide range of sterically and electronically varied maleimides. The regioselectivity and molecular structures of representative adducts were confirmed by single-crystal X-ray diffraction. This operationally straightforward, additive-enabled protocol provides a powerful platform for the site-selective diversification of pharmacologically relevant quinoxalinone scaffolds, offering synthetic versatility and mechanistic insight into Ru(II)-catalyzed C–H alkylation chemistry.