Continuous-Flow Asymmetric Hydrogenation for the Synthesis of an (S)-Metolachlor Intermediate Using Catalysts Immobilized on a Core/Shell-Type Support

Here we show continuous-flow synthesis of a key inter-mediate of (S)-Metolachlor, which is a widely used agrochemical that is in huge demand, with asymmetric hydrogenation using a heterogeneous catalyst immobilized on a core/shell-type support. We have immobilized a homogeneous catalyst onto a core/shell-type heterogeneous support that was developed in our laboratory, which showed high turnover frequency and turnover number over a long period (over 120 h) when used in a solvent-free continuous-flow manner. This result demonstrates the feasibility of continuous-flow production of chiral agrochemicals with packed-bed heterogeneous catalysts. Moreover, the heterogenization protocol was shown to be applicable to elaborate practical catalysts used in industry, especially the group of phosphine ligands.