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

• Zachary G. Brill, Casey B. Ritts, Umar Faruk Mansoor, Nunzio Sciammetta

• Department of Discovery Chemistry, MRL, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115 USA

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.

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