Continuous Flow Enables Metallaphotoredox Catalysis in a Medicinal Chemistry Setting: Accelerated Optimization and Library Execution of a Reductive Coupling between Benzylic Chlorides and Aryl Bromides

• DOI: 10.1021/acs.orglett.9b04117
• Publication Date: 2019-12-27T17:57:40Z
• Authors: Zachary G. Brill; Casey B. Ritts; Umar Faruk Mansoor; Nunzio Sciammetta
• Keywords: 01 natural sciences; 3. Good health; 0104 chemical sciences

Continuous flow has been used widely in process chemistry and academic settings for various applications. However, initial reaction discovery has generally remained "batch-exclusive" despite the existence of efficient, reproducible flow systems. We hereby disclose a workflow to bridge the gap between early medicinal chemistry efforts and process-scale development, showcased by the discovery and optimization of a metallaphotoredox-catalyzed cross-coupling between benzylic chlorides and aryl bromides, followed by two library syntheses of complex drug-like compounds.