Continuous-Flow Synthesis and Derivatization of Aziridines through Palladium-Catalyzed C(sp3)−H Activation

• Published in: Angewandte Chemie (International ed.) Vol. 55; no. 31; pp. 8878 - 8883
• Main Authors: Zakrzewski, Jacek, Smalley, Adam P., Kabeshov, Mikhail A., Gaunt, Matthew J., Lapkin, Alexei A.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 25.07.2016; Wiley; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: aziridines; Chemistry; Chemistry, Multidisciplinary; Communication; Communications; continuous-flow synthesis; C−H activation; palladium catalysis; Physical Sciences; ring opening; Science & Technology; aziridines; palladium catalysis; REACTORS; continuous-flow synthesis; DIRECT ARYLATION; MECHANISM; SAFE; H BOND FUNCTIONALIZATION; CLAISEN REARRANGEMENT; C-H activation; ring opening; CHEMISTRY; METAL; BATCH; TECHNOLOGY; C−H activation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201602483

A continuous‐flow synthesis of aziridines by palladium‐catalyzed C(sp3)−H activation is described. The new flow reaction could be combined with an aziridine‐ring‐opening reaction to give highly functionalized aliphatic amines through a consecutive process. A predictive mechanistic model was developed and used to design the C−H activation flow process and illustrates an approach towards first‐principles design based on novel catalytic reactions. Keep up with the flow! A predictive mechanistic model was developed and used to design a flow process for C−H activation. The resulting continuous‐flow synthesis of aziridines through palladium‐catalyzed C(sp3)−H activation was combined with ring opening of the aziridine in flow to give highly functionalized aliphatic amines in a consecutive process involving the capture and release of the aziridine intermediate (see scheme).