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

Abstract

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.

Increasing Catalyst Efficiency in C−H Activation Catalysis

“…Palladium-catalyzed aziridine synthesis. [46] Scheme 18. Pd-catalyzed dehydrogenative alkyne-heteroarene coupling.…”

Recent Applications of Continuous Flow in Homogeneous Palladium Catalysis

“…34 In 2016, Lapkin et al reported a successful translation of palladium-catalysed C(sp 3 )-H activation forming aziridines into a practical flow process (Scheme 24). 35 The optimisation of the flow process was based on a previous batch reaction 36 and mechanistic studies. Thus, flow palladium-catalysed C-N bond-forming reactions on a hindered aliphatic amine using an in-line work-up (catch and release protocol) provided the corresponding aziridine derivative in a significantly shortened reaction time and an increased spacetime yield.…”

Synergistic Manganese(I) C−H Activation Catalysis in Continuous Flow: Chemoselective Hydroarylation

“…In addition, we designed ac onvenient separation [19] strategy for the manganese catalyst (Scheme 6b), thus clearly highlighting the advantages of the flow approach for the removal and recycling of the manganese catalyst. In addition, we designed ac onvenient separation [19] strategy for the manganese catalyst (Scheme 6b), thus clearly highlighting the advantages of the flow approach for the removal and recycling of the manganese catalyst.…”