Marnix van der Kolk

Visible-light-driven fluorination reactions have been widely developed in recent years. This review highlights recent advances in visible-light-mediated C–F bond formation, providing efficient strategies for the synthesis of a wide range of fluorinated compounds.

Fluorine is a widely used structural element in chemistry and has been utilized in diverse fields, including organic chemistry and pharmaceuticals. Fluorine's diverse applications have led to the development of numerous fluorination reaction methods. Visible-light-assisted reactions have attracted significant interest and development in organic chemistry due to their advantages in reaction conditions and efficiency. In particular, visible-light-driven fluorination has been recognized as a valuable synthetic strategy, resulting in the production of numerous fluorinated compounds. This review presents a summary of recent developments in visible-light-driven fluorination reactions developed since 2021.

Hydrogen bonding provided by pinacol or 2-trifluoromethyl-2-propanol enhances the selectivity of nucleophilic fluorination of several secondary alkyl bromides or mesylates.

Synthesis of secondary alkyl fluorides via nucleophilic substitution faces the problem of high competition with E2 processes. This competition depends on the chemical environment of the substrate, the counterion, and the hydrogen bonding to the fluoride ion. Herein, we combined reliable theoretical calculations and experimental studies to probe the reactivity and selectivity of different substrates. The calculations have shown the significance of S _N 2 versus E2 competition in various chemical environments. In the experiments, we have tested the use of potassium fluoride combined with 18-crown-6 and the bulky alcohols pinacol and 2-trifluoromethyl-2-propanol (TBOH-F3) with several alkyl bromides and mesylates. The combination of tetrabutylammonium fluoride (TBAF) with these alcohols was also evaluated. We have found that potassium fluoride, combined with the crown ether and the bulky alcohols, is more selective than TBAF combined with these alcohols, although TBAF is more reactive. Alkyl mesylates are less prone to the formation of E2 products, and high fluorination yields can be obtained when using KF (potassium fluoride) combined with 18-crown-6 and pinacol in acetonitrile solvent. We have also identified 2-bromo-1-phenylpropane as a very challenging substrate. Even when using a high concentration of 1,1,1,3,3,3-hexafluoro-2-propanol in acetonitrile solution, fluorination of this substrate was not achieved.

This review highlights hypervalent iodine (HVI) chemistry combined with light or electricity as a sustainable platform for radical fluorination and fluoroalkylation. It systematically classifies key developments in photo- and electrochemical HVI-mediated transformations, emphasizing reaction design, mechanistic insights, and the synergistic role of HVI reagents.

Fluorine incorporation profoundly influences the physicochemical and biological properties of organic molecules, yet conventional fluorination often relies on hazardous reagents and harsh conditions. Recent advances have established hypervalent iodine (HVI) chemistry, combined with light or electricity, as a sustainable platform for radical fluorination and fluoroalkylation under mild, redox-neutral conditions. This review highlights key developments in photo- and electrochemically driven HVI-mediated transformations, systematically classified by the number of fluorine atoms introduced—mono-, di-, and trifluoromethyl/perfluoroalkylation. Emphasis is placed on reaction design, mechanistic insights, and the synergistic role of HVI reagents in enabling efficient, selective, and environmentally benign synthesis of organofluorine compounds.

Materials made from nylon 6 are widely used but difficult to recycle back into their original monomer, ε-caprolactam. This work introduces a simple acid-catalyzed alcoholysis method that enables efficient and selective depolymerization of nylon 6 into ε-caprolactam. Additionally, this process shows excellent compatibility with a range of real-world nylon 6 materials, including post-consumer fishing net waste, thread, 3D-printing filament, fabric, and carpet, offering a practical pathway toward closed-loop recycling with both environmental and economic benefits.

This work describes an efficient, straightforward protocol for the direct incorporation of fluorinated cyclopropyl moieties via energy-transfer catalysis. The method unlocks access to a broad range of previously inaccessible fluorocyclopropyl compounds in good yields. Mechanistic insights, supported by DFT calculations, elucidate the reactivity and guide further synthetic applications.

This study presents an efficient and straightforward method for the direct incorporation of fluorinated cyclopropyl moieties via energy-transfer catalysis. The approach leverages the reactivity of a diverse range of oxime esters functionalized with fluorinated cyclopropyl groups, enabling the selective formation of the desired products under mild conditions.

Nature Synthesis, Published online: 24 March 2026; doi:10.1038/s44160-026-01035-2

An oxidative activation strategy using pyridyl phosphonium salts and potassium persulfate is reported. This approach, which governs the reaction pathway, enables the synthesis of C4-fluorinated and C4-trifluoromethylaminated pyridines with a broad functional group tolerance and is used for the late-stage synthesis and modification of bioactive molecules.

Nature, Published online: 20 March 2026; doi:10.1038/d41586-026-00937-7

Nature staff discuss some of the week’s top science news.

Nature Chemistry, Published online: 13 March 2026; doi:10.1038/s41557-026-02096-8

Fluorochemicals improve our quality of life, but there is an increasing concern over their production and the negative impact on health and the environment. Now chemical recycling of fluorochemicals via base-induced defluorination has been demonstrated, and the resulting potassium fluoride has been used to synthesize organic and inorganic compounds.

This study proposes a versatile strategy for synthesizing high-valence metal single atoms on nitrogen-carbon supports via coordination with electronegative fluorine atoms, forming an asymmetric planar M-N₂F₂ configuration. This configuration induces an asymmetric polarized spin effect that stabilizes metal atoms in high-spin/high-valence states, thereby effectively suppressing atomic aggregation and enhancing catalytic stability.

ABSTRACT

High-valence single-atom catalysts (HVSACs) generally exhibit superior catalytic activity owing to the fast electron transfer efficiency between HVSACs and their supportive substrate. Nevertheless, the thermodynamically unstable HVSACs are prone to spontaneous aggregation during their conventional synthesis processes, largely limiting their practical application demanding long-term stability. Herein, we demonstrate a universal approach to synthesize stable HVSACs by incorporating high-electronegativity fluorine (F) atoms to directly coordinate with the targeted metal atoms (M) of HVSACs on nitrogen-carbon supports. As a result, an asymmetric planar M-N₂F₂ structure is introduced, which boosts asymmetric polarized spin between M and F atoms with M stabilized at their high-spin and high-valence state. Leveraging this motif, we further demonstrate its high universality as a promising synthetic approach by obtaining stable HVSACs for 22 individual metal elements. Using high-valence Mn single-atom as a model system, the resulting MnN₂F₂ catalyst exhibits not only high activity but also superior durability in both the oxygen reduction reaction (ORR) and practical Zn–air batteries, outperforming conventional MnN₄ single atoms.

We present a high-throughput selection system to engineer fluoroacetate dehalogenases (FAcDs). By challenging E. coli populations that produce diverse FAcD libraries to grow on non-natural organofluorides as their sole carbon source, we isolated a panel of FAcD variants with improved activity and altered substrate specificity.

ABSTRACT

The widespread use of organofluorides in modern society has inadvertently led to the bioaccumulation of harmful pollutants, most prominently per- and polyfluorinated alkyl substances (PFAS). In principle, tailored biocatalysts able to cleave C─F bonds represent an attractive strategy to combat this (emerging) environmental crisis. However, Nature is largely impartial to C─F bonds, with fluoroacetate dehalogenases (FAcDs) standing out by catalyzing the hydrolysis of single C─F bonds in fluoroacetate at high turnover rates. To harness its catalytic prowess for non-natural organofluorides, we designed and applied a robust growth-based selection strategy for large-scale FAcD engineering. Specifically, we demonstrate that FAcD-catalyzed C─F bond cleavage of (natural and) synthetic organofluorides generates metabolizable carbon sources for bacteria, enabling in vivo enrichment of active FAcD variants. By forcing populations expressing diverse FAcD-libraries to utilize various organofluorides as sole carbon source, we elicited a panel of FAcD variants with improved activities and altered substrate profiles for fluoroacetate, 2-fluoropropionate, and 2,2-difluoroacetate. In these efforts, we also identified a previously overlooked inhibition pathway, which impedes the conversion of gem-difluoride compounds. Overall, our study presents the first large-scale engineering campaign of FAcDs and introduces an operationally simple selection platform to adapt these enzymes for the sustainable degradation of contaminating organofluorides.

While traditional photoredox catalysis is highly dependent on bimolecular collisions between the excited photoredox catalyst and substrate, in this work, we introduce a strategy that integrates a chromophore directly into the substrate, significantly enhancing substrate activation and reducing precursor loading. By exploiting the dual properties of the chromophore as both a photocatalyst and a charged leaving group, we not only accelerate the reaction rate but also simplify the purification step. Application of this approach is further demonstrated by the synthesis of 18F-labeled arenes containing PET tracers.

In this article, we have successfully developed an electrochemical method for synthesizing N-aryl ketoamides from α-ketoacids and arylamines. This approach utilizes direct electron transfer in the presence of electrolyte ions and a phosphine reagent to achieve deoxygenative amidation, preserving both carbonyl groups.

α-Ketoacids serve as sustainable acylating agents due to their α-ketoacid functionality. While decarboxylative amidation under metal, photoredox, or electrochemical catalysis have been established, deoxygenative amidation pathways remain relatively rare—especially electrochemically mediated variants. Herein, we report an electrochemical method for synthesizing N-aryl ketoamides from α-ketoacids and arylamines. This approach utilizes direct electron transfer in the presence of electrolyte ions and a phosphine reagent to achieve deoxygenative amidation, preserving both carbonyl groups. The operationally simple and oxidant-free protocol provides efficient access to diverse ketoamides.

Nature, Published online: 23 February 2026; doi:10.1038/s41586-026-10263-7

Markovnikov hydroamination of terminal alkenes via phosphine redox catalysis

An approach for the difluorinative acetonylation of imidazo[1,2-a]pyridines using selectfluor and aryl methyl ketones has been described. The formation of two C-F bonds and one C-C bond was achieved through this method. The method has been successfully extended to benzimidazothiazole derivatives.

We have developed an approach for the geminal difluorinative vicinal acetonylation of imidazo[1,2-a]pyridines using selectfluor and aryl methyl ketones. This strategically designed nucleophilic addition of aryl methyl ketone to imidazopyridine was achieved through the geminal difluorination of imidazo[1,2-a]pyridine using selectfluor. The method resulted in the formation of two CF bonds, one CC bond, and a quaternary stereocenter. This mild, efficient, and cost-effective method offers a broad substrate scope and successfully extended to benzimidazothiazole derivatives.

Song and co-workers report a nucleophilic, C-5-regioselective halogenation of pyridines via an in situ dearomatization-rearomatization strategy. The commercial availability of halogenating reagents—imidoyl halides—and operational simplicity endow this method with practical value. This nucleophilic halogenation strategy can serve as a beneficial complement to existing electrophilic or radical meta-halogenation methods for pyridines.