Jonas Wuyts

Nature, Published online: 09 June 2025; doi:10.1038/d41586-025-01775-9

Simulated lab accidents train students how to respond to real emergencies.

Hydrogenation reactions are well-established transformations in both homogeneous and heterogeneous catalysis and are increasingly explored using single-atom catalysts (SACs). Despite this progress, a comprehensive understanding of the underlying reaction mechanisms remains limited, often restricted to specific systems. Moreover, the precise nature of the active sites is elusive, and their reactivity may be influenced by varying coordination numbers, hetero-atom doping, and other factors. To gain insight into hydrogenation reactions in nitrogen-doped graphene-based SACs, we conducted a thorough investigation into hydrogen transfer across Fe, Co, Mn, and Ru systems, considering different charges, spin states, pyrrolic and pyridinic sites. Our findings reveal substantial deviation from conventional homogeneous and heterogeneous systems, with SACs being strongly influenced by the nature of the active site. Analyses using Natural Bond Orbitals (NBO), natural charge, and NEDA highlighted differences in nitrogen-metal interactions as a key factor driving the observed reactivity variations between Pyrr and Py systems, as well as between Ru and 1st-row metals.

The current draft of the global plastics treaty suggests that biodegradable plastics have the potential to end plastic pollution (1). This perception, combined with ever-rising consumer demand, has fueled biodegradable plastic production, which reached 2.47 million tonnes in 2024 and is projected to hit 5.73 million tonnes by 2029 (2). However, the widespread adoption of biodegradable plastics could pose ecological risks that must be addressed.

Nature Chemistry, Published online: 05 June 2025; doi:10.1038/s41557-025-01824-w

Moses Dike and Shudipto Konika Dishari explore lignin’s historic journey alongside human civilization and showcase its game-changing potential to drive sustainability without compromising performance.

Nature, Published online: 04 June 2025; doi:10.1038/s41586-025-09068-x

This study presents a nuclear magnetic resonance-based method to determine local structure and bonding of Pt single-atom catalysts.

The Front Cover illustrates the transformation of α-angelica lactone into high-value molecules through three types of catalysis. α-Angelica lactone is an economical and versatile five-membered heterocycle obtainable from lignocellulosic biomass. Its name derives from its natural occurrence in the roots of Angelica archangelica, an aromatic medicinal plant historically used in traditional remedies, which also has a long-standing tradition in European cuisine. Its stems and roots are aromatic, with a flavor reminiscent of licorice, anise, and wild fennel. Starting from this same key ingredient, lactone-organocatalytic, metal-catalyzed, and biocatalytic asymmetric processes enable the synthesis of new chiral enantioenriched butenolide-containing heterocycles. More information can be found in the Review by A. Moutayakine, S. Meninno, and A. Lattanzi (DOI: 10.1002/cctc.202500060). The cover was designed by Luca Meninno.

In this study, we developed a new strategy for the synthesis of long-chain dicarboxylic acid ester precursors via the aldol condensation of 2,5-diformylfuran (DFF) and methyl levulinate (MLA) in the presence of protic ionic liquids. The reaction mechanism was further investigated using nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR).

Abstract

In this study, a series of long-chain dicarboxylic acid ester precursors were synthesized via aldol condensation reactions catalyzed by protic ionic liquids (PILs). When 2,5-diformylfuran (DFF) and methyl levulinate (MLA) were employed as substrates, the yield of long-chain dicarboxylic acid ester precursors reached 91.0% in the presence of pyrrolidine lactate. This preparation process eliminated the need for additional acids and bases, thereby minimizing the generation of waste salts, which was a common issue in base-catalyzed systems and biosynthesis methods. Nuclear magnetic resonance (NMR) characterization revealed that a strong interaction between the hydroxyl group of the catalyst and the carbonyl group of MLA facilitated the activation of the substrate for the aldol condensation reaction. Notably, the yield of dicarboxylic acid ester precursors remained stable even after five catalytic cycles, demonstrating the excellent reusability of the catalyst. Furthermore, pyrrolidine lactate exhibited broad applicability in both aldol condensation and Knoevenagel condensation reactions. This work presented a novel and sustainable strategy for the synthesis of long-chain dicarboxylic acid ester precursors.

Nature, Published online: 23 May 2025; doi:10.1038/d41586-025-01228-3

Artificial intelligence is perfect for teaching novices, but less good for experts. Use it with that in mind, says Hannah Hackney.

Nature, Published online: 20 May 2025; doi:10.1038/s41586-025-09159-9

One-carbon homologation of alkenes

Publication date: 12 June 2025

Source: Chem, Volume 11, Issue 6

Author(s): Chang-Sheng Kuai, Yang Yuan, Xiao-Feng Wu

A robust, automated continuous flow system enables safe, high-yield nitration of furfural to key nitrofuran intermediates using in situ acetyl nitrate generation. Demonstrated on representative essential World Health Organization (WHO) active pharmaceutical ingredients (API), this innovative open-source platform ensures rapid synthesis, enhanced safety, and excellent reproducibility, aligning with modern pharmaceutical standards.

Abstract

Nitrofurfural is a key building block for the synthesis of antimicrobial nitrofurans as active pharmaceutical ingredients. Its synthesis involves the nitration of furfural, a substrate derived from biobased resources. However, furfural has a delicate heteroaromatic backbone. Typical nitrations involve harsh reaction conditions, which often compromise this structure, resulting in poor reproducibility and low yields. Although acetyl nitrate, a mild nitrating agent, is suitable for this task, major deterrents remain. First, its conventional preparation method involves conditions that are not compatible with furfural. Second, significant safety concerns are associated with the unstable and explosive nature of acetyl nitrate. These critical issues are addressed herein. A safe and robust continuous flow platform featuring in situ generation of acetyl nitrate for the nitration of furfural to nitrofurfural is reported. The high level of integration and automation enables remote process operation by a single operator. Key furfural-based pharmaceutical intermediates were synthesized with favorable metrics and high reproducibility. The efficiency of this flow platform is demonstrated using a selection of best-selling nitrofuran pharmaceuticals (nifuroxazide, nifurtimox, nitrofurantoin, and nitrofural), which were obtained with excellent isolated yields in under five minutes.

Ketones are highly valued for their ability to engage in numerous functional group interconversions. However, the synthesis of complex ketones is traditionally limited by the need to employ organometallic reagents or pre-synthesize an activated component. Herein, we report a photoredox-catalyzed, double deoxygenative fragment coupling of alcohols and carboxylic acids that provides rapid access to sp3-rich ketone scaffolds. We further highlight new avenues for C1 logic through a bis-radical SOMO stitching approach that delivers ketone products from two alcohol substrates.

Visible light-driven photochemistry has advanced significantly, offering diverse methodologies in synthetic organic chemistry. Photocatalysis using red and near-infrared (NIR) light is particularly notable due to its lower energy, reduced phototoxicity, minimized side reactions, and deeper penetration into reaction media. This minireview summarizes recent developments in red- and NIR-mediated photocatalysis, emphasizing radical generation and reactive intermediates for organic synthesis. Applications in small-molecule activation, polymer chemistry, and biologically relevant transformations are discussed, highlighting the growing potential of these photochemical processes in fundamental and applied chemistry.

Abstract

The field of visible light-mediated photochemistry has experienced significant growth, leading to the development of a wide array of methodologies in synthetic organic chemistry. In particular, photocatalysis by using long-wavelength light such as red and near-infrared (NIR) light has garnered substantial attention. These strategies have inherent benefits of low energy, including minimal health hazards, less side reactions, and increased penetration through diverse reaction media. In this minireview, we present an overview of recent advancements in red- and NIR light-induced photocatalysis for the generation of various radicals and key intermediates in organic synthesis. Additionally, this minireview will recount the application of small-molecule activation, polymer science, and bio-related aspects to offer a comprehensive framework and insight of photochemistry mediated by red and NIR light.

In this review, we describe synthetic methods that harvest fluoride (F–) from fluorocarbons and deliver it to other molecules through either transfer fluorination or fluoride shuttling. We also summarise related approaches, transfer hydrofluorination and HF shuttling in which hydrogen fluoride (HF) is generated in situ from one fluorocarbon and used to prepare another, along with recent breakthroughs in fluoroalkene cross-metathesis. Our focus is on reactions that can be applied to industrially relevant fluorochemicals, namely refrigerants (HFCs and HFOs) and fluoropolymers (PTFE, PVDF, PVF). We provide insight into the mechanisms that break and remake carbon–fluorine bonds as part of linear reaction sequences or catalytic manifolds. Limitations of the current methodologies are highlighted and opportunities for future developments discussed.

Piperidine and pyridine are highly prominent nitrogen heterocyclic motifs in pharmaceuticals and of high relevance. The direct reduction of flat pyridines into piperidines with high sp3-carbon content is of strong appeal producing high-value products and broadening structural space. However, direct hydrogenation of pyridines with homogenous catalysts is challenging due to its aromatic stability and catalyst-poisoning abilities. We describe a robust and selective iridium(III)-catalyzed ionic hydrogenation of pyridines to corresponding functionalized piperidines. Important highly reduction-sensitive groups including nitro-, azido-, bromo-, alkenyl- and alkynyl are inert enabling access to a broad range of multi-substituted piperidines in high yields, substantially expanding the available chemical space for this relevant scaffold. The method requires low catalyst loadings, is scalable to decagrams, and delivers the most synthetically valuable free secondary amines as easily isolable and stable piperidinium salts. Applied in a complex late-stage setting, the pyridine motif in several FDA-approved drugs were successfully and selectively hydrogenated.

The production of fluorochemicals is currently achieved through a linear manufacturing process starting from fluorspar (CaF2). While fluorochemicals improve our quality of life, there is increasing concern over their negative impact on health and the environment. Here we report an approach to preparing fluorine-containing molecules through recycling. Treatment of hydrofluorocarbons (HFCs) with a potassium base (KHMDS, KOtBu, KBn) results in rapid defluorination to produce anhydrous potassium fluoride. The scope of fluorochemicals that can be recycled includes industrially relevant HFCs, hydrofluoroolefins (HFOs), fluoroethers – including anaesthetics and battery additives, perfluorooctanoic acid (PFOA), and poly(vinylidene difluoride) (PVDF). The in situ generated potassium fluoride harvested from these materials can then be used to prepare a wide range of fluorinated organic and inorganic molecules.

Introduction of alkyl substituents onto nucleophilic nitrogen atoms in amines is a central synthetic strategy for increasing molecular complexity and structural diversity in medicinal chemistry, organic synthesis, and materi-als science. Although the direct transfer of a stereogenic alkyl group onto a nitrogen atom by N-alkylation is one of the most efficient approaches to asymmetric C(sp3)–N bond formation, few methods are available for the enan-tioconvergent N-alkylation of amines with racemic alkyl transfer reagents. We report herein, a previously unex-plored enantioconvergent decarboxylative N-alkylation of aromatic amines with racemic carboxylic acids. The reaction is enabled by a merger of acridine photocatalysis with Co(salen)-catalyzed asymmetric radical–polar crossover (RPC). The study provides a simple synthetic segway to medicinally and synthetically valuable α-chiral benzylic amines and elucidates the structural, electronic, and bonding effects that govern the stereocontrol imparted by the privileged Co(salen)-based asymmetric RPC catalytic system.

Recent rapid developments in forest biomass valorisation have highlighted lignin as a key value driver for the economic sustainability of modern biorefining. Sugar-based biorefinery hydrolysis lignin (HL) from wood biomass has an immense potential as an alternative for fossil-based aromatic feedstock. However, impurities, heterogeneous structures and limited solubility in common solvents are the main challenges associated with HL functionalisation. Aqueous organic solvent fractionation represents a promising approach to improve on HL properties and subsequently increase its valorisation options. In this study, for the first time, biorefinery HL derived from birch was purified and fractionated with water-EtOH and -THF mixtures across the whole co-solvent concentration range at ambient temperature. The highest lignin solubility was achieved with 70 wt% THF mixture, which dissolved a remarkable 81 wt% of lignin available in HL. Moreover, fractionated lignin purity was further increased to 95 wt% when employing an extra water-washing step. In general, fractions soluble in THF mixtures had high dispersity, syringyl-to-guaiacyl (S/G) subunit ratio and aliphatic OH-groups, whereas EtOH fractions had narrower molecular weight distributions, lower S/G subunit ratio and higher concentration of phenolic OH-groups. A brief description of the solvent effects at the molecular level was given using molecular dynamics simulations which revealed specific solvation between the dissolved lignin and solvent mixture. Protocol presented in this paper enables to purify HL and control the physicochemical properties of the soluble lignin fractions by simply altering the composition of the solvent mixture, and therefore, expanding the possibilities in valorisation of HL.

Nature, Published online: 23 April 2025; doi:10.1038/s41586-025-08751-3

A transparent and reproducible scientific framework is introduced to formalize how trillions in economic losses are attributable to the extreme heat caused by emissions from fossil fuel companies, which could inform climate liability claims.

The conversion of lignin toward value-added products relies on the cleavage of C─C and C─O bonding patterns, which has proven to be a difficult task previously, with numerous factors at play. The employment of model compounds which are fashioned on the structure and linkages found within lignin aids in the development of catalytic processes which can then be applied for the scission of linkages within native lignin. This review focuses on the strategies which have been used for the synthesis and conversion of key model compounds of lignin and the products obtained following their breakdown studies.

Abstract

The push toward a renewable society where the chemicals being used on a daily basis come from sources which are not going to be depleted within the next few decades is highly sought after. Biomass is one of the most promising opportunities to establish self-sustainability for the human race. This review article takes a look at some of the key methods which have been employed for the synthesis of important lignin model compounds, and the synthetic techniques are discussed throughout the first section. The second section of this review is focused on some of the major strategies for the conversion of lignin model compounds throughout the literature. This review serves as a good starting point for someone who is relatively new to the field of lignin model synthesis and valorization.

The reductive hydroformylation of olefins can be catalyzed by Rh which is immobilized on a highly branched amine containing polymer for efficient recycling and a high selectivity and alcohol yield.

Abstract

The reductive hydroformylation of olefins is an important process in the chemical industry to produce alcohols directly without isolating the aldehydes as intermediates. As the hydroformylation is a homogeneously catalyzed reaction, the catalyst recycling and down-stream processing is often complex and energy intensive. A heterogeneous reductive hydroformylation catalyst was developed in this work by immobilizing Rh on polymeric amine macroligands to form solid molecular catalysts (SMCs). An iterative macroligand improvement was carried out by increasing the basicity and number of amine groups at the immobilization sites. With the best performing SMC, olefins were fully converted to >99% alcohols without a hydrogenation of the substrate in a solvent free environment, thus requiring only a separation of the heterogeneous catalyst to yield the pure product. The catalyst was successfully recycled over 12 runs with a perpetual Rh leaching as low as 1.2%, and the metal to macroligand ratio was identified as most important parameter in reducing metal loss.

We investigated the continuous, tandem catalytic reductive hydroformylation of 1-octene in a segmented slug flow reactor using a single catalyst enabled by CO degassing. Higher alcohols are of significant industrial importance and are traditionally produced through a two-step process. The use of rhodium-based catalysts offers advantages in terms of activity and selectivity towards linear alcohols; however, carbon monoxide (CO) inhibits catalytic activity in the subsequent reduction step. An innovative approach is presented here, where CO is selectively removed from the reaction mixture after hydroformylation utilizing a semi-permeable AF2400 membrane in a tube-in-tube setup to enhance reaction efficiency. The results demonstrated a notable improvement in yields, achieving 67.1% yield of l-nonanol with an impressive linear-to-branched (l/b) ratio of 10.6 after a residence time of only 27.6 minutes. This study highlights the significance of effective degassing and demonstrates the potential for sustainable optimization of reductive hydroformylation in continuous flow operations, showcasing that nearly full conversion can be achieved under optimized conditions with comparatively low catalyst loading of 0.5 mol.-%.