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Synthesis
DOI: 10.1055/a-2557-7635
DOI: 10.1055/a-2557-7635
short review
Bürgenstock Special Section 2024 – Future Stars in Organic Chemistry
Carbamoyl Fluorides: A Platform to Interrogate Fluoride-Enabled Reactivity
This work was financially supported by the Natural Sciences and Engineering Council of Canada (NSERC) Discovery (RGPIN-2021-03630) and CREATE (575259-2023) Grant Programs.
Abstract
The strong and polar nature of C–F bonds impart organofluorine compounds with highly desirable properties, making them indispensable in pharmaceutical, agrochemical, and polymer research. While this bond strength makes the modification of organofluorine compounds challenging, it also creates opportunities for the development of innovative strategies for their functionalization. Carbamoyl fluorides represent an emerging class of fluorinated electrophiles, showcasing unique fluoride-enabled reactivity and serving as versatile building blocks for accessing valuable amides and heterocyclic compounds. This review highlights recent progress in the synthesis and reactivity of carbamoyl fluorides, including comparisons to their chlorinated counterparts where relevant.
1 Introduction
2 Synthesis and Simple Nucleophilic Substitution Reactions of Carbamoyl Fluorides
2.1 Direct Use of Difluorophosgene
2.2 Use of (Di)fluorophosgene Equivalents
2.2.1 From Isocyanates and Thioformamides
2.2.2 From Amines
2.3 Use of Difluorocarbene Sources
2.4 Use of CO2 and Deoxyfluorinating Reagents
2.5 Miscellaneous Methods
3 Reactivity of Carbamoyl Fluorides
3.1 Covalent Inhibition of Enzymes
3.2 Nucleophilic Substitution
3.3 Transition-Metal-Catalyzed C–F Bond Activation
3.4 Lewis Acid and Base Catalyzed Carbamoylation
4.0 Outlook and Conclusion
Key words
fluorine - carbamoyl fluoride - fluoride-enabled reactivity - carbamoylation - C–F bond functionalization - difluorocarbene - fluorophosgenePublication History
Received: 27 January 2025
Accepted after revision: 13 March 2025
Accepted Manuscript online:
13 March 2025
Article published online:
28 April 2025
© 2025. Thieme. All rights reserved
Georg Thieme Verlag KG
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