An efficient biocatalytic oxidative dehydroaromatization approach for the construction of quinolines enabled by monoamine oxidase with molecular oxygen

Abstract

Quinolines are important building blocks for the synthesis of natural products and pharmaceuticals. In comparison with classical methods, dehydroaromatization of 1,2,3,4-tetrahydroquinolines has emerged in recent years as an efficient and straightforward way to access quinolines due to its high atom economy and sustainability. However, existing chemical methods suffer from the use of transition metal catalysts and harsh reaction conditions. Herein, we report a novel biocatalytic route for the efficient oxidative dehydrogenation of 1,2,3,4-tetrahydroquinolines employing monoamine oxidase from Pseudomonas putida KT2440 (PpMAO) with molecular oxygen, affording the corresponding quinolines with moderate to excellent yields (up to 99%) combined with the adjustment of the microenvironment for deprotonation and the supplied amount of molecular oxygen. Unlike other common one-step aromatizations of N-heterocycles, mechanism studies have suggested that PpMAO-catalyzed aromatization involves at least two-step C–N bond dehydrogenation reactions. The first step is the formation of an imine intermediate catalyzed by enzymes, followed by enzyme-mediated aromatization in the second step. Furthermore, preparative-scale biotransformation of tetrahydroquinolines was successfully demonstrated with good isolated yields (up to 95%). This system not only provided an efficient and facile method for the synthesis of quinolines under mild conditions but also enriched the redox biocatalytic approaches to N-heterocycles.