Tomas Horsten

Electrocatalytic hydrogenation (ECH) of furfural under acidic conditions is examined using Pd/C and Pd-TiON_x/GO catalysts. Differences in redox behavior and adsorption properties are observed. Pd/C exhibits higher selectivity toward furfuryl alcohol, while Pd-TiON_x/GO favors 2-methylfuran formation. Metal–support interactions and surface properties are shown to play a key role in tuning ECH activity and selectivity.

Electrocatalytic hydrogenation (ECH) offers a sustainable alternative to conventional hydrogenation of biomass-derived compounds by using cathodic potential instead of heat and molecular hydrogen. This study explores the ECH of furfural under acidic conditions, focusing on how metal–support interactions influence the performance of Pd-based catalysts. Two systems are compared: Pd on carbon (Pd/C) and Pd supported on titanium oxynitride-graphene oxide (Pd–TiONx/GO). Pd–TiONx/GO exhibits lower oxophilicity and a higher proton adsorption tendency than Pd/C. Additionally, its surface shows a more negative charge, indicated by a cathodic shift (≈10 mV) in the potential of zero total charge measured via N₂O reduction. These differences significantly affect catalytic behavior. While Pd/C shows roughly twice the activity for converting furfural to furfuryl alcohol (FA), Pd–TiONx/GO is over 100 times more active in producing 2-methylfuran (2-MF) and also enhances the competitive hydrogen evolution reaction. This suggests Pd–TiONx/GO has lower surface coverage by furfural and FA, allowing for more hydrogen adsorption and favouring 2-MF formation. Overall, the study demonstrates that Pd's electrosorptive and catalytic properties can be tuned via electronic effects from the TiONx support, enabling selective manipulation of ECH pathways.

A flow electrolyzer employing formate dehydrogenase on a porous TiO₂-carbon felt cathode is developed for paired electrolysis of CO₂ and waste (plastic and biomass) to produce formate. The electrolyzer operates with an initial cell faradaic efficiency toward formate of almost 200% at a low cell voltage of −1.5 V, which also enables bias-free operation with a commercial solar cell. The electrogenerated formate is used directly for photocatalytic carbon chain extension of styrene to phenylpropanoic acid.

Abstract

Paired electrolysis enables the simultaneous coupling of CO₂ reduction with anodic waste upcycling to form valuable products. However, achieving selective, efficient, and stable product formation and coupling to downstream valorization remains a challenge. In this study, W-containing formate dehydrogenase from Nitratidesulfovibrio vulgaris Hildenborough is immobilized onto a cathode made from carbon felt coated with porous TiO₂ and paired with a commercial Ni foam anode to assemble a semiartificial flow electrolyzer for the simultaneous conversion of CO₂ and waste (plastic and biomass) to the single product formate. The enzymatic flow electrolyzer achieved an initial cell faradaic efficiency toward formate of almost 200%, a maximum CO₂ conversion yield of 18% and can operate at a low full-cell voltage of −1.5 V for 122 h, which allows for bias-free operation with a silicon photovoltaic cell. The aqueous formate produced in the enzymatic electrolyzer was subsequently utilized downstream as a C₁ building block in the photocatalytic hydrocarboxylation of alkenes, providing a path for the domino valorization of CO₂ and waste toward bulk and fine chemical synthesis.

Strong nucleophiles play an important role in catalysis and CO₂ conversion. In this work the emerging versatile roles of 4-aminopyridines in CO₂ conversion, ranging from structural elements to catalytic components, are discussed with an eye to their interaction with CO₂ and mechanistic aspects.

Abstract

Organic superbases are a family of compounds endowed with high nucleophilicity and basicity. Several powerful nucleophiles such as DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene), or DMAP (4-dimethylaminopyridine) are involved in CO₂ conversion but their catalytic roles may differ from a mechanistic standpoint. In this work, we show the versatile application of 4-aminopyridines in CO₂ fixation leading to products of CO₂ reduction as well as cyclic carbonates and fine chemicals. In such cases, 4-aminopyridines serve not just as organocatalysts, but as recurring motifs performing as bases, structural components, ligands for electronic modulation of metals and full-fledged catalytic components. Such roles are highlighted herein with an eye to the understanding of mechanistic aspects and the interaction between 4-aminopyridines and CO₂ through the discussion of several catalytic studies.

A rapid synthesis of azosulfones can be accomplished in a vibrational mechanical mill, giving up to quantitative yields in as little as 30 min. The tolerance of the method is demonstrates on a broad substrate scope and is successfully used to produce 30 different products. Spectroscopic and computational studies provide insight into the process and its selectivity.

Azosulfones represent a potent and stable surrogate for diazonium salts. Their wide application in C–H functionalizations catalyzed by transition metals and visible light is well-known in organic chemistry. Here, a single-step mechanochemical synthesis of azosulfones is reported, starting from readily available precursors, which has high conversion efficacy −80%–99% isolated yields are obtained in most cases. A substrate scope of 30 different compounds is obtained. This method requires no solvent, it is quick and has potential in terms of scalability and tolerance toward a broad range of functional groups, which makes it attractive for synthesis. Spectroscopic and computational studies are performed to explain the observed reactivity patterns.

This study investigates continuous synthesis of 2-methoxyhydroquinone (MHQ) from vanillin in a Taylor-Couette disc contactor (TCDC). The TCDC, a stirred column reactor utilizing Taylor vortices for intense mixing, achieved efficient phase separation and hydraulic stability. With an 83% yield, 93.8% purity, and a production rate of 0.55 kg h⁻¹ of MHQ, the product proves suitability for redox flow batteries.

Organic redox flow batteries are a promising sustainable technology for large-scale storage of surplus energy in the grid. However, the main challenge lies in scaling up the synthesis of redox-active molecules from sustainable sources, as either the synthesis is complex or renewable feedstock is not available at a large scale. This challenge is addressed by employing vanillin, a fine chemical widely available from lignin, as a starting material for the synthesis of redox-active hydroquinones. The use of a continuously operating column reactor, known as the Taylor-Couette disc contactor, is demonstrated to generate redox-active 2-methoxyhydroquinone in high yields and purity. Production rates of ≈0.55 kg h⁻¹ of 2-methoxyhydroquinone are achieved, with sufficient purity for use in single-cell redox flow battery performance and short-stack stability tests.

Synthetic methods that are applicable to a broad range of substrates are sought after, owing to their utility in industrial settings. This minireview describes considerations associated with how chemists define and identify general methods, especially with the emergence of modern analytical, high-throughput, and data science tools in chemistry, and gives the reader an overview of workflows that have been used to expedite this pursuit.

Abstract

The term “generality” has recently been popularized in synthetic chemistry, owing largely to the increasing use of high-throughput technology for producing vast quantities of data and the emergence of data science tools to plan and interpret these experiments. Despite this, the term has not been clearly defined, and there is no standardized approach toward developing a method with a diverse (general) scope. This minireview will examine different emerging strategies toward achieving generality using selected examples and aims to give the reader an overview of modern workflows that have been used to expedite this pursuit.

Nature Chemistry, Published online: 02 September 2025; doi:10.1038/s41557-025-01904-x

Underexplored atom swap reactions offer the opportunity to selectively edit organic molecules and to streamline lead discovery and optimization in the pharmaceutical and agrochemical industry. Now it has been shown that benzimidazoles can be accessed from indoles via C-to-N atom swap. The method was applied to 15 drug-like indoles.

The first organocatalytic enantioselective [4 + 4] cycloaddition of furan ortho-quinodimethanes is presented. The reaction proceeds in good yields and with high enantioselectivities allowing for the formation of novel classes of cyclooctanoids. DFT calculations point to an intriguing mechanism, where the stereochemical outcome is attributed to protonation of the catalyst-bound intermediate in the stereo-determining step.

Abstract

The enantioselective [4 + 4] cycloaddition for the construction of cyclooctanoids is a challenging transformation in organic chemistry. Herein, we present the first organocatalytic enantioselective [4 + 4] cycloaddition of furan ortho-quinodimethanes, activated by dearomatization of the heteroaromatic compound, which thereby allows for the cycloaddition with dienes. The [4 + 4] cycloaddition is catalyzed by a quinine-derived primary amine in combination with a chiral phosphoric acid and a carboxylic acid affording cyclooctanoids isolated as a single diastereoisomer in good yields and with up to 94% ee. This reaction concept allows for the formation of cyclooctanoids without benzofusion, as demonstrated by oxidative opening of the furan ring. Computational studies of the reaction mechanism for the [4 + 4] cycloaddition point to a stepwise process. Surprisingly, the stereochemical outcome of the reaction is attributed to protonation of the two organocatalyst-bound cyclooctanoid intermediates leading to a preferred set-up for catalyst elimination to account for the absolute configuration of the cyclooctanoid.

Electrochemical decarboxylative acetoxylation of Fmoc-protected peptides via anodic oxidation of the carboxylic acid is challenging under conventional conditions, due to the lability of the Fmoc protecting group. Using selected cosolvents which can be oxidized at higher potentials than the target carboxylic acid but lower than the protecting group, the electrochemical acetoxylation is enabled under constant current conditions.

The synthesis of peptide-based linkers for antibody-drug conjugates involves an oxidative decarboxylation step. Traditional Hofer–Moest electrolysis conditions are not suitable to achieve this transformation due to the presence of an oxidatively labile Fmoc-protecting group. Herein, a solvent-enabled electrochemical procedure has been established, whereby the solvent electrochemical window prevents degradation of the protecting group. The method has been demonstrated for several relevant peptides in good to very good yields (64–92%).

Nature, Published online: 26 August 2025; doi:10.1038/s41586-025-09551-5

Scalable total synthesis of saxitoxin and related natural products

A continuous-flow electrochemical C–H amination strategy enables efficient and scalable synthesis of (hetero)arylamines from electron-rich and electron-deficient arenes via a pyridination–aminolysis sequence. The method avoids strong oxidants and metal catalysts, delivering over 100 grams of product with broad substrate scope and excellent functional group tolerance.

Abstract

The direct C─H amination of arenes is a powerful strategy for synthesizing arylamines, yet existing methods often suffer from limited substrate scope, poor selectivity, or scalability issues, particularly for electron-deficient arenes. Here, we introduce a continuous flow electrochemical C─H amination via a pyridination-aminolysis sequence, enabling the efficient functionalization of arenes with diverse electronic properties. The method operates under continuous flow electrochemical conditions, avoiding the need for divided cells, strong chemical oxidants, or homogeneous transition-metal catalysts. The broad substrate scope includes a wide range of electron-rich, electron-deficient, and halogenated arenes, as well as heterocycles, demonstrating excellent functional group tolerance. Furthermore, the process is readily scalable, as shown by a 4-day continuous operation in parallel microreactors, producing over 100 grams of aniline product with high efficiency. This study highlights the potential of continuous-flow electrochemistry as a versatile and practical platform for sustainable C─H functionalization in organic synthesis.

Science, Volume 389, Issue 6760, Page 556-556, August 2025.

We report a multicomponent reaction involving an aryl halide, an aldehyde, and a silane derivative, facilitated by low-valent bismuth redox catalysis under mild conditions. The protocol represents an unprecedented example of four elementary organometallic steps at a Bi center within the catalytic cycle. Experimental and computational studies indicate the involvement of intermediate species that supports a Bi(I)/Bi(III) cycle.

Abstract

Herein, we report a catalytic defluorinative arylation of aldehydes with (per) A fluoroarenes facilitated by a pincer-based PheBox-Bi(I) under mild conditions. The protocol features various novel aspects in bismuth redox catalysis; namely, (1) a catalytic 1,2-aryl migratory insertion to forge a C─C bond, (2) an unprecedented example of multicomponent reaction through four elementary organometallic steps at a Bi center, (3) an unusual strategy for Bi(I) compounds regeneration via O─Si reductive elimination. Experimental and computational studies aided in dissecting the various mechanistic aspects of the bismuth redox cycle.

Nature, Published online: 06 August 2025; doi:10.1038/d41586-025-02485-y

Researchers have developed an AI-enhanced hydrogel capable of sticking even in wet, salty conditions.

The direct functionalization of abundant and readily available feedstock chemicals has emerged as a powerful strategy to rapidly increase molecular complexity and access valuable scaffolds. Herein, we report a novel photocatalyzed three-component oxo-amidomethylation of aromatic olefins under aerobic conditions, enabling the synthesis of N-(γ-oxopropyl)amides via simultaneous incorporation of two orthogonal functional groups across the alkene C═C bond in a single step. Mechanistic features include the photocatalyzed hydrogen atom transfer (HAT)-mediated engagement of the α-N-alkyl C(sp³)–H bond in cost-effective amides and the trapping of a key olefin-derived carbon-centered radical intermediate by molecular oxygen to afford the oxo-functionalized homologated products. This cascade protocol demonstrates compatibility with a broad range of aryl olefins and amides, as well as efficient scalability. The method provides streamlined access to high-value molecular architectures of synthetic and pharmaceutical relevance without the need for pre-functionalized radical precursors.