Customizing continuous chemistry and catalytic conversion for carbon–carbon cross-coupling with 3dP

Abstract

Abstract Support structures of various materials are used to enhance the performance of catalytic process chemistry. Typically, fixed bed supports contain regular channels enabling high throughput because of the low pressure drop that accompanies high flow rates. However, many fixed bed supports have a low surface-area-to-volume ratio resulting in poor contact between the substrates and catalyst. Three dimensional polymer printing (3dP) can be used to overcome these disadvantages by offering precise control over key design parameters of the fixed bed, including total bed surface area, as well as accommodating system integration features that are compatible with continuous flow chemistry. Additionally, 3dP allows for optimization of the catalytic process based on extrinsic constraints (e.g. operating pressure) and digital design features. These design parameters together with the physicochemical characterization and optimization of catalyst loading can be tuned to prepare customizable reactors based on objectives for substrate conversion and desired throughput. Using a Suzuki (carbon–carbon) cross-coupling reaction catalyzed by palladium, we demonstrate our integrated approach. We discuss key elements of our strategy including the rational design of hydrodynamics, immobilization of the heterogeneous catalyst, and substrate conversion. This hybrid digital-physical approach enables a range of pharmaceutical process chemistries spanning discovery to manufacturing scale.