An Immobilized-Dirhodium Hollow-Fiber Flow Reactor for Scalable and Sustainable C-H Functionalization in Continuous Flow

Abstract

A scalable flow reactor is demonstrated for enantioselective and regioselective rhodium carbene reactions (cyclopropanation and C-H functionalization) by developing cascade reaction methods employing a microfluidic flow reactor system containing immobilized dirhodium catalysts in conjunction with the flow synthesis of diazo compounds. This allows the utilization of the energetic diazo compounds in a safe manner and the recycling of the dirhodium catalysts multiple times. This approach is amenable to application in a bulk-scale synthesis employing asymmetric C-H functionalization by stacking multiple fibers in one reactor module. The products from this sequential flow-flow reactor are compared with a conventional batch reactor or flow-batch reactor in terms of yield, regioselectivity, and enantioselectivity.

Keywords: C−H functionalization; diazo transfer; flow chemistry; hollow fiber reactor; rhodium.