Marnix van der Kolk

We report a Cu(I)-photocatalyzed three-component coupling process to achieve the regioselective, vicinal 1,2-aminosulfonylations of alkenes. The critical aspect of this methodology is found in the utilization of in situ generated photoactive Cu(I)-amine substrate com-plexes, which facilitate the formal oxidation of Cu(I) to Cu(III) in a stepwise manner. In this way, the conceivable two-component chlorosulfonylation of alkenes is effectively suppressed, allowing the combination of styrenes, sulfonyl chlorides, and amines. Further-more, this protocol can be used to facilitate late-stage functionalization, thereby enabling the diversification of biomolecules

Nature, Published online: 02 April 2025; doi:10.1038/d41586-025-01019-w

The Dreamer system reached the milestone by ‘imagining’ the future impact of possible decisions.

An alkylative carbosulfonylation protocol for the formation of C-S and C-C bonds between sulfinate salts and readily available alkenes under visible light irradiation is reported. This approach formally couples two alkene molecules to give access to highly functionalized sp3 sulfone products following two sequential radical additions. Homocoupled and polarity mismatched cross-coupled products were obtained. The utility of the methodology is highlighted by further transformations of the novel sulfone products.

The Chemputer, a universal chemical robotic platform, automates the synthesis of molecular machines, addressing the labor-intensive nature of current methods. By integrating on-line NMR and liquid chromatography within the XDL programming language, complex syntheses are standardized, improving reproducibility and efficiency. As a demonstration, we report the autonomous synthesis of [2]rotaxanes with real-time monitoring for reaction control and purification. By streamlining key challenges, the Chemputer enables broader automation in chemistry, freeing researchers to pursue more ambitious and exploratory work.

Nature, Published online: 26 March 2025; doi:10.1038/s41586-025-08698-5

This study highlights a protocol that converts various perfluoroalkyl and polyfluoroalkyl substances (PFASs), including fluoroplastics, into valuable fluorochemicals through a solvent-free mechanochemical process, thereby enabling fluorine recovery and contributing to a sustainable circular fluorine economy.

We discussed here the recent developments on the abundant transition metal based photocatalysts and their applications in red light-driven photocatalysis.

Abstract

Photocatalysis emerges as an efficient and versatile tool for the preparation of organic compounds via the development of new methodologies and new photosensitizers. Mostly UV and blue light irradiation are used for such reactions. Red light is low-energy light, it is less harmful and has more penetration depth. Hence red light-driven photocatalysis would be more suitable for preparing value-added products. Red-absorbing photosensitizers are mostly based on rare and expensive metals. In this review, we describe the recent developments on Earth-abundant transition metal-based photosensitizers (W(0), Mo(0), Cr(0), Fe(III), Cu(I), Zn(II)) and their applications in red light-driven photocatalysis. Photocatalysis using both electron transfer and energy transfer processes is discussed. Three different red light-induced reactions such as direct monophotonic excitation, sensitized triplet-triplet annihilation upconversion (sTTA-UC), and dual red light photocatalysis are presented. Various organic transformations such as reductive dehalogenation and detosylation, reduction of diazonium salts, C─C coupling via C─H activation, oxidation of aryl boronic acids to phenols, polymerization reactions, cross dehydrogenative couplings, α-cyanation of tertiary amines, Barton decarboxylation have been carried out using abundant photosensitizers and red light.

Chiral phosphoric acids (CPAs) and their derivatives play a crucial role in various fields. Traditional synthesis of axial chiral organophosphorus compounds (OPCs) from white phosphorus (P4) involves a multi-step, environmentally hazardous chlorination pathway via P4 → PCl3 → OPCl3 → OPCs. Zhang and co-workers have developed a chlorine-free method for synthesizing CPAs and their derivatives from P4. This environmentally friendly and low-waste method directly utilizes P4 as the phosphorus source to construct diverse valuable axially chiral OPCs, bypassing the traditional multi-step, toxic PCl3-based routes.

Nature, Published online: 26 March 2025; doi:10.1038/s41586-025-08698-5

This study highlights a protocol that converts various perfluoroalkyl and polyfluoroalkyl substances (PFASs), including fluoroplastics, into valuable fluorochemicals through a solvent-free mechanochemical process, thereby enabling fluorine recovery and contributing to a sustainable circular fluorine economy.

Nature Synthesis, Published online: 25 March 2025; doi:10.1038/s44160-025-00771-1

Despite the abundance and non-toxic nature of sodium, organosodium reagents have rarely been used in organic synthesis. Now iron-catalysed homocoupling and C(sp2)–C(sp3) cross-coupling reactions of arylsodium compounds are reported. The observed C(sp2)–C(sp3) cross-coupling reactivity of arylsodium reagents is enabled by Lewis donor additive N,N,N′,N′-tetramethylethylenediamine.

The valorization of renewable materials is critical to improving the circularity of the chemical industry. This Synergy article describes how lignin waste streams can be upgraded to valuable resources through reductive catalytic depolymerization. The article presents the challenges linked to the upscaling of this process and offers guidelines for performing the process in a successful and economic manner.

This review describes eleven fluorine-containing drugs approved by the US FDA in 2024. The review discusses the synthetic methodologies employed, the structural characteristics of these drugs, and their clinical implications, providing insights into the ongoing innovation within the pharmaceutical industry driven by fluorine chemistry.

Abstract

Fluorine has become an essential element in the development of modern pharmaceuticals, due to its unique chemical properties that can significantly enhance the biological activity, metabolic stability, and lipophilicity of drug molecules. This review explores recent advancements in the synthesis and application of fluorine-containing drugs approved by the US Food and Drug Administration (FDA) in 2024. These novel drugs demonstrate improved efficacy and safety profiles, addressing a range of therapeutic areas including oncology, infectious diseases, metabolic disorders and genetic disorders that affect the adrenal glands. The incorporation of fluorine atoms into drug candidates has facilitated the development of molecules with optimized pharmacokinetic and pharmacodynamic properties, leading to better patient outcomes. The review further discusses the synthetic methodologies employed, the structural characteristics of these drugs, and their clinical implications, providing insights into the ongoing innovation within the pharmaceutical industry driven by fluorine chemistry.

Metathesis and reversible catalytic reactions are fundamentally intriguing and powerful tools in modern synthetic chemistry. While most reversible catalytic reactions are predicated on breaking and forming reactive functional groups, the ability to leverage the C–H bond as a functional group into metathesis reactions has proved to be exceptionally challenging. Here, we develop a C–H/C–X metathesis reaction through a radical swapping protocol where a hydrogen and halogen are traded between molecules via reversible hydrogen atom transfer (HAT) and halogen atom transfer (XAT) that allows for mild C–H halogenation. The reversibility of this process allows for selective dehalogenation of polyhalogenated products to form monohalogenated products. Leveraging the reversibility of this process, halogenated organic pollutants can also serve as a halogen source for C–H halogenation. In the broader context, this work establishes that incorporating reversible metathesis logic in C–H bond functionalization can provide complementary advantages in synthetic strategies.

A metal-free electrochemical method for the chlorination of terminal C(sp³)─H bonds of alkanes is described. The specific cavity size of organic molecular catalysts ensures high regioselectivity, while the use of inexpensive and readily reusable graphite felt electrodes, a simple electrochemical device, and mild conditions enables the reaction to maintain good efficiency even when applied in flow electrochemistry and used for kilogram-scale production.

Abstract

Although research on the activation of C─H bonds in alkanes has been ongoing for decades, there are still few strategies that are both highly selective and suitable for industrial production. Herein, we report a highly selective method for the chlorination of terminal C─H bonds in alkanes by combining electrochemistry and organocatalysis. The specific cavity size of organic molecular catalysts ensures high regioselectivity, while the use of inexpensive and readily reusable graphite felt electrodes, a simple electrochemical device, and mild conditions enables the reaction to maintain good efficiency even when applied to kilogram-scale production.

https://www.shs-conferences.org/articles/shsconf/abs/2024/24/shsconf_diges-grace2024_04004/shsconf_diges-grace2024_04004.html

Nature Chemistry, Published online: 11 March 2025; doi:10.1038/s41557-025-01769-0

N-monofluoromethyl amides (N-CH2F) have been challenging to prepare. Now, a general method for the synthesis of N-CH2F amides is developed. The strategy can be applied for the N-CH2F modification of peptides and drug derivatives. Moreover, the N-CH2F amides are relatively stable in various media, which could be beneficial for drug development.

Playing video games is a popular recreational activity and a cyber sport. Is it possible to translate video gaming into chemical education? Below I present ChemChallenge - the first video game with in-game currency and non-linear gameplay (not a quiz game) for studying and teaching thermodynamics.

Nature, Published online: 11 March 2025; doi:10.1038/d41586-025-00729-5

Experts weigh in on the risks of moderate drinking — and how people should assess them.