Flow electrochemistry: a safe tool for fluorine chemistry.

Bethan Winterson,Tim Rennigholtz,Thomas Wirth

doi:10.1039/d1sc02123k

Bethan Winterson, Tim Rennigholtz + Show 1 more

Open Access

https://doi.org/10.1039/d1sc02123k

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Abstract

The heightened activity of compounds containing fluorine, especially in the field of pharmaceuticals, provides major impetus for the development of new fluorination procedures. A scalable, versatile, and safe electrochemical fluorination protocol is conferred. The strategy proceeds through a transient (difluoroiodo)arene, generated by anodic oxidation of an iodoarene mediator. Even the isolation of iodine(iii) difluorides was facile since electrolysis was performed in the absence of other reagents. A broad range of hypervalent iodine mediated reactions were achieved in high yields by coupling the electrolysis step with downstream reactions in flow, surpassing limitations of batch chemistry. (Difluoroiodo)arenes are toxic and suffer from chemical instability, so the uninterrupted generation and immediate use in flow is highly advantageous. High flow rates facilitated productivities of up to 834 mg h−1 with vastly reduced reaction times. Integration into a fully automated machine and in-line quenching was key in reducing the hazards surrounding the use of hydrofluoric acid.

Highlights

The construction of carbon– uorine bonds in organic molecules is an upsurging eld in chemical synthesis, which still presents ongoing difficulties for organic chemists
A broad range of hypervalent iodine mediated reactions were achieved in high yields by coupling the electrolysis step with downstream reactions in flow, surpassing limitations of batch chemistry. (Difluoroiodo)arenes are toxic and suffer from chemical instability, so the uninterrupted generation and immediate use in flow is highly advantageous
The yield of the hypervalent iodine reagent was inferred by the yield of 2a, given the puri cation oftoluene is more hazardous than 2a

Summary

Introduction

The construction of carbon– uorine bonds in organic molecules is an upsurging eld in chemical synthesis, which still presents ongoing difficulties for organic chemists. A broad range of hypervalent iodine mediated reactions were achieved in high yields by coupling the electrolysis step with downstream reactions in flow, surpassing limitations of batch chemistry. In order to foster a sustainable approach, the batch electrochemical synthesis of (di uoroiodo)arenes has been subject to ongoing investigation (Fig. 1).[14] For example, the electrochemical uorocyclisation of N-allylcarboxamides, uorodesulfurisation of dithioacetals and uorination of a-dicarbonyl compounds was the subject of elegant work by Waldvogel14a and Fuchigami.14c,d While the selectivity and yields of the products were generally high, the substrate types amenable were limited because success was typically contingent on in-cell applications.

Results

Conclusion