Manganese-Catalyzed Regioselective Hydroboration of Quinolines via Metal–Ligand Cooperation

Abstract

Selective reduction of readily available N-heteroarenes is important in both organic synthesis and chemical biology. Herein, we describe ligand-controlled regiodivergent hydroboration of quinolines using well-defined amido–manganese catalysts, with an emphasis on the rarely reported 1,4-regioselectivity. Mechanistic studies showed that 1,2-hydroboration of quinoline was kinetically favorable and reversible, whereas 1,4-hydroboration was under thermodynamic control. Using a 1-methyimidazole-based pincer amido–manganese complex as the catalyst, cooperative C–H···N and π···π noncovalent interactions between the 1-methyimidazole moiety and quinoline substrates enabled kinetic accessibility of 1,4-hydroboration, giving thermodynamically favored 1,4-hydroborated quinolines as the major products. On this basis, Mn-catalyzed 1,4-hydroboration of a series of substituted quinolines proceeded smoothly in high yields. A high turnover number of 2500 was achieved in this reaction with satisfying regioselectivity. This transformation could be further applied to the C3-selective functionalization of quinolines, highlighting the synthetic utility of this methodology. In contrast, using a pyridine-based pincer amido–manganese complex as the catalyst, which lacked the C–H···N interaction, the free-energy barrier for 1,4-hydroboration significantly increased through a N–B···N interaction between the “HMn–NB” species and quinoline, resulting in the kinetically favored 1,2-hydroboration product with excellent regioselectivity.