A novel strategy for catalyzing the functionalization of C(sp3)-H in 2- methylquinoline derivatives using amino acids

Abstract

• Amino acid-catalyzed the functionalization of C(sp 3 )-H was conducted. • The addition of amino acids significantly improved the reaction efficiency. • The yield achieved 91.47 % after only 36 h of reaction. • The recycling experiment demonstrated that L-Leu exhibited excellent reusability. Using amino acids as catalysts, the addition reactions between four quinolone derivatives (2-methylquinoline, 2,4-dimethylquinoline, 2,6-dimethylquinoline, and 2,7-dimethylquinoline) and p -nitrobenzaldehyde ( p -NBA) were conducted, respectively. Thin layer chromatography (TLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR) analysis confirmed that the functionalization reaction occurred exclusively on the methyl group at C-2 position of the quinoline ring. The addition of amino acids, particularly the L-leucine, significantly improved the reaction efficiency. By optimizing the conditions, the yield of 1-(4-nitrophenyl)-2-(quinoline-2-yl)ethane-1-ol ( IIIa ) achieved 91.47 % after only 36 h of reaction. The proposed catalytic mechanism suggested that amino acids mediated the electron transfer process via hydrogen bonding, which facilitated the rearrangement reaction of double bonds, and promoting the formation of enamine intermediates. The recycling experiments demonstrated that the L-Leu could be effectively recovered and reused solely through filtration, thereby enhancing the practical value of this method.