Recent developments of monofluorination via three-component reactions

The incorporation of fluorine into organic molecules holds significant value. The three-component reaction provides a more convenient approach for the synthesis of organofluorine compounds. Radical monofluorination will be fully discussed in this review. Besides, other methods like transition metal-catalyzed, electrophilic, nucleophilic and carbine-mediated conditions will also be discussed. There are two main methods for producing monofluorinated compounds: forming C–F bonds using fluorinating agents, or creating C–C bonds with fluorinated substrates. The latter method boasts a wider range of applicable substrates. We will discuss reactions involving various substrates, including NFSI, KHF2, Selectfluor, FABI, Et3N·3HF, COF2, ICH2F, DAST and others. We will review the advancements made over the past decade (2014-2024) and offer explanations of the underlying mechanisms.

Publication History

Received: 10 April 2025

Accepted after revision: 20 May 2025

Accepted Manuscript online:
20 May 2025