Chemoselective Aerobic C3-Hydroxylation of Tetrahydroquinolines Catalyzed by a Hydrophobic Ni–Mn Hybrid Interface

Abstract

Controlling the chemoselectivity of aerobic oxidation of 1,2,3,4-tetrahydroquinolines (THQs) remains challenging because these substrates typically undergo preferential dehydrogenative aromatization to quinolines. Here we report a homologous series of linear carboxylate-modified hydrophobic Ni–Mn organic–inorganic hybrids, among which the n-hexanoic acid-derived HA-Ni2Mn emerged as the optimal catalyst for redirecting THQ oxidation from conventional dehydrogenative aromatization to dehydrogenative C3-hydroxylation. Under 1 atm O2, HA-Ni2Mn converts diverse THQ derivatives to 3-hydroxyquinolines in up to 89% yield. Correlation analysis across the acid-treated, structurally homologous catalyst series indicates that fixed-time conversion and product yield exhibit the strongest empirical correlations with apparent surface hydrophobicity, whereas C3-hydroxylation selectivity is more closely associated with redistribution of the surface basic-site population. Together with the Mn electronic-structure analysis, these trends are consistent with a cooperative interfacial redox/basic environment that redirects the reaction toward C3 oxygenation. This additive-free heterogeneous protocol accommodates a structurally diverse set of benzo-fused THQ derivatives, gram-scale applicability, and utility in the concise synthesis of dye intermediates and pharmaceutically relevant 3-hydroxyquinoline scaffolds.