Finn Moeller

We report an efficient continuous-flow electroreductive nickel-catalyzed cyclopropanation of olefins using commercial gem-dichloroalkanes. The reaction is tolerant to oxygen and moisture while displaying a broad functional group compatibility. This methodology enables gram-scale cyclopropanation and is compatible with a wide range of alkenes. Mechanistic studies suggests that a nickel carbene is electro-generated to afford the cyclopropane ring.

Abstract

Cyclopropanes are valuable motifs in organic synthesis, widely featured in pharmaceuticals and functional materials. Herein, we report an efficient electrochemical methodology for the cyclopropanation of alkenes, leveraging a nickel-catalyzed process in continuous-flow. The developed protocol demonstrates broad substrate scope, accommodating both electron-rich and electron-poor alkenes with high functional group tolerance. Beyond dichloromethane as a feedstock methylene source, the methodology enables the synthesis of methylated, deuterated, and chloro-substituted cyclopropanes. Mechanistic investigations suggest the electro-generation of a nickel carbene as key intermediate. Notably, the reaction operates under ambient conditions, tolerates air and moisture, and achieves scalability through continuous-flow technology, offering a straightforward route to multi-gram quantities with enhanced throughput.

Nature, Published online: 31 January 2025; doi:10.1038/d41586-025-00328-4

Researchers with lived experience of the chronic workplace stress that typifies burnout describe how they sought help and turned their working lives around.

YES WE CAN—the electrochemical iodination of electron-deficient arenes under Lewis acid-free conditions in a divided cell is realized when Bu₄NI as pre-reagent is oxidised at the anode and catalytic amounts of Bu₄NCl are present for the generation of [I₂Cl]⁺ as active iodinating agent. The iodination is capable to convert a wide range of interesting halogenated arenes, aromatic aldehydes, benzoic acids, benzoates, aryl nitriles, aryl ketones and nitrobenzene derivatives into their corresponding iodinated products.

Abstract

The iodination of electron-deficient arenes and heteroarenes is a long-standing problem in organic synthesis. Herein we describe the electrochemical iodination in nitromethane with Bu₄NI as iodine source and supporting electrolyte under Lewis acid-free conditions in the presence of small amounts of chloride anions. The electrochemically generated reagent could be applied for the iodination of halogenated arenes, aromatic aldehydes, acids, esters, ketones, as well as nitroarenes to afford the products in good to excellent yields.

A general and efficient method for the organo-mediated electrooxidative cyclopropanation of unactivated alkenes with methylene compounds has been developed. The method shows excellent functional group tolerance and a broad substrate scope that can be extended to late-stage modification of biorelevant compounds.

Abstract

Cyclopropanes are prevalent in natural products, pharmaceuticals, and bioactive compounds, functioning as a significant structural motif. Although a series of methods have been developed for the construction of the cyclopropane skeleton, the development of a direct and efficient strategy for the rapid synthesis of cyclopropanes from bench-stable starting materials with a broad substrate scope and functional group tolerance remains challenging and highly desirable. Herein, we present an electrochemical method for the direct cyclopropanation of unactivated alkenes using active methylene compounds. The strategy shows a broad substrate scope with a high level of functional group compatibility, as well as potential application as demonstrated by late-stage cyclopropanation of complex molecules and drug derivatives. Further mechanistic investigations suggest that Cp₂Fe (Fc) plays an essential role as an oxidative mediator in generating radicals from active methylene compounds.

Organofluorine compounds bearing the hexafluoroisopropyl group remain extremely scarce due to the lack of appropriate fluoroalkylation reagents. Herein we report a molecular photoelectrocatalysis method for the C−H hexafluoroisopropylation of indoles and tryptophan peptides, utilizing hexafluoro-2-propanol (HFIP) as the fluoroalkylation reagent.

Abstract

Despite the increasing interest in radical-based fluoroalkylation techniques, the organofluorine compounds bearing the partially fluorinated hexafluoroisopropyl group remain extremely scarce due to the lack of appropriate reagents. Herein we report an unprecedented photoelectrocatalytic method for the C−H hexafluoroisopropylation of indoles and tryptophan peptides, utilizing the readily available hexafluoro-2-propanol (HFIP) as the fluoroalkylation reagent. In this process, HFIP is converted into hexafluoroisopropyl radicals, enabling fluoroalkylation reactions. This study broadens the potential applications of molecular photoelectrocatalysis, highlighting its capacity to enable transformations that are difficult to accomplish through traditional electrochemical or photochemical approaches.

Nature, Published online: 20 January 2025; doi:10.1038/d41586-024-04253-w

Survey of more than 1,600 biomedical researchers also flagged small sample sizes and cherry-picking of data as leading causes of reproducibility problems.

The Cover Feature refers to the sustainability of furanic platform chemicals and their derivatives, which are derived from renewable plant materials. It also shows the schematic color profiles of these derivatives′ stability in various solvents. The systematic study of the stability of furanic compounds allows us to assess the feasibility of conducting reactions with these substances under specific reaction conditions. More information can be found in the Research Article by V. P. Ananikov and co-workers (DOI: 10.1002/cssc.202401849). Cover created by Anastasia Golysheva.

Nature Communications, Published online: 17 January 2025; doi:10.1038/s41467-025-56138-9

Accidental ingestion of Pb-contaminated soils represents a major route of Pb exposure for humans. Here, the authors show an effective and straightforward approach of drinking cola beverages to reduce blood Pb levels following the ingestion of contaminated soils based on animal models data.

Nature, Published online: 17 January 2025; doi:10.1038/d41586-025-00125-z

Two researchers, one with bipolar disorder and ADHD, the other with autism, discuss supportive workplaces, building networks, and how and when to disclose diagnoses.

The stereocontrolled hydrogenation of ketones by dual iridium catalysis was demonstrated. The finding that N,P−Ir (active towards alkenes) and NHC,P−Ir (active towards ketones) can perform the asymmetric hydrogenation under the same conditions (solvent, pH, hydrogen source) while exhibited complementary chemoselectivity was key to the development of this methodology. By simple choice of chirality on each iridium complex, each stereoisomer of the alcohol could separately be prepared with precise control over the absolute stereochemistry.

Abstract

The concept of dual catalysis is an emerging area holding high potential in terms of preparative efficiency, yet faces severe challenges in compatibility of reaction conditions and interference of catalysts. The transition-metal catalyzed stereoselective hydrogenation of olefins and ketones typically proceeds under different reaction conditions and/or uses a different reductant. As a result, these two types of hydrogenations can normally not be performed in the same pot. Herein, the stereocontrolled hydrogenation of enones to saturated alcohols is described, enabled by orthogonal dual iridium catalysis, using molecular hydrogen for both reductions. In this one-pot procedure, N,P-iridium catalysts (hydrogenation active towards olefins) and NHC,P-iridium catalysts (hydrogenation active towards ketones) operated independently of one another allowing the construction of two contiguous stereogenic centers up to 99 % ee, 99/1 d.r. Ultimately, by simple selection of the chirality of either ligands, the enone could be efficiently reduced to all four stereoisomers of the saturated alcohol in equally high stereopurity. This degree of stereocontrol for the synthesis of different stereoisomers by dual transition-metal catalyzed hydrogenation was previously not attained. The generality in substituted enones (alkyl, aryl, heteroaryl) demonstrate the wide applicability of this concept.

The NiRu hybrid electrocatalyst with enhanced phenol adsorption, increased para-benzoquinone (p-BQ) desorption, and suppressed oxygen evolution capabilities, simultaneously achieves excellent phenol abatement and valuable p-BQ production at ambient conditions.

Abstract

Electrocatalytic oxidation of aqueous phenol to para-benzoquinone (p-BQ) offers a sustainable approach for both pollutant abatement and value-added chemicals production. However, achieving high phenol conversion and p-BQ yield under neutral conditions remains challenging. Herein, we report a Ni(OH)₂-supported Ru nanoparticles (NiRu) hybrid electrocatalyst, which exhibits a superior phenol conversion of 96.5 % and an excellent p-BQ yield of 83.4 % at pH 7.0, significantly outperforming previously reported electrocatalysts. This exceptional performance benefits from the triple synergistic modulation of the NiRu catalyst, including enhanced phenol adsorption, increased p-BQ desorption, and suppressed oxygen evolution. By coupling a flow electrolyzer with an extraction-distillation separation unit, the simultaneous phenol removal and p-BQ recovery are realized. Additionally, the developed electrocatalytic system with the NiRu/C anode displays good stability, favorable energy consumption, and reduced greenhouse gas emissions for phenol-containing wastewater treatment, demonstrating its potential for practical applications. This work offers a promising strategy for achieving low-carbon emissions in phenol wastewater treatment.

The fully exposed and atomically dispersed Ru clusters composed by an average of 3 Ru atoms were successfully fabricated and exhibited robust catalytic performance in the multi-step hydrogenation of toluene to methylcyclohexane, compared with Ru single atoms, Ru nanoparticles and even previously reported catalysts. The theoretical calculations revealed that the synergetic interaction among neighboring Ru atoms in the fully exposed cluster guarantees effective activation of the reactant and easy desorption of the product.

Abstract

Liquid organic hydrogen carriers (LOHCs) are attractive platform molecules that play an important role in hydrogen energy storage and utilization. The multi-step hydrogenation of toluene (TOL) to methylcyclohexane (MCH) has been widely studied in the LOCHs systems, due to their relatively low toxicity and reasonable hydrogen storage capacity. Noble metal catalysts such as Ru has exhibited good performance in multi-step hydrogenation reactions, while the application is still hindered by their high cost and low specific activity. Therefore, the primary challenge lies in the development of noble metal catalysts with both robust activity and efficient atomic utilization. In this study, a series of Ru species ranging from single atoms, fully exposed clusters to nanoparticles were fabricated to investigate their structural evolution in the TOL multi-step hydrogenation reaction. The fully exposed and atomically dispersed Ru clusters, composed of an average of 3 Ru atoms, exhibit superior catalytic performance and recycle ability in TOL multi-step hydrogenation. Moreover, it delivers a high turnover frequency of 9850.3 h⁻¹ under the relatively mild reaction (100 °C, 1.5 MPa), compared with those of single atoms and nanoparticles, and shows a notable advantage over catalysts reported in previous studies. From density functional theory (DFT) calculations, the overall barrier of the TOL multi-step hydrogenation reaction over the fully exposed Ru clusters is significantly lower than that of single atoms and nanoparticles, resulting in its higher activity. The present work provides an efficient strategy to regulate the reaction pathway of multi-step complicated catalytic reactions by designing fully exposed metal cluster catalysts.

A direct anodic oxidative coupling process for α-heteroarylation using ferrocene-assisted asymmetric nickel electrocatalysis has been developed, enabling the synthesis of a diverse range of chiral heteroaromatic carbonyl compounds with high enantioselectivity and functional group tolerance, which can be applied to the synthesis of valuable frameworks like (−)-COX-2 inhibitor, (+)-acremoauxin A, and (+)-pemedolac.

Abstract

Oxidative cross-dehydrogenative C−H/C−H functionalizations represent an exemplary approach for synthesizing carbonyl compounds via α-heteroarylation. Here we present the development of a direct anodic oxidative coupling process between 2-acylimidazoles and divergent heterocyclic systems including indole, pyrrole, and furan, facilitated by ferrocene-assisted asymmetric nickel electrocatalysis with high levels of enantioselectivity. Mechanistic investigations indicate that the reaction initially involves the formation of a chiral Ni-bound α-carbonyl radical, which is then captured by the heteroarene radical cation via intermolecular stereoselective radical/radical cation coupling. The mild, scalable, and robust reaction conditions allow for a broad substrate scope and excellent functional group tolerance, enabling access to a wide range of chiral hetero-compounds. The consequential α-heteroaromatic carbonyl products can potentially be transformed into a plethora of synthetically valuable frameworks, as exemplified by their application in the asymmetric total synthesis of (−)-COX-2 inhibitor, (+)-acremoauxin A, and (+)-pemedolac.

Nature, Published online: 13 January 2025; doi:10.1038/d41586-024-04241-0

A study highlights how public-health researchers are targeted for focusing on tobacco, alcohol and ultra-processed foods.

A modular approach for the first catalytic asymmetric total syntheses of (+)-chamaecydin and (+)-isochamaecydin and their 1’,5’-epimers is presented. Our synthesis is highlighted by a metal-halogen exchange/addition reaction to connect the A−B ring system with E ring system through a convergent strategy and a Michael/aldol cascade for constructing the central C−D ring system, allowing for a rapid construction of the pentacyclic framework.

Abstract

A modular approach was developed for the first catalytic asymmetric total syntheses of naturally occurring C₃₀ terpene quinone methides and their non-natural stereoisomers, which feature the presence of an unprecedented spiro[4.4]nonane-containing 6–6–6-5–5–3 hexacyclic skeleton. Resting on a chiral phosphinamide-catalyzed enantioselective reduction of 2,2-disubstituted cyclohexane-1,3-dione, a concise route for the synthesis of enantioenriched 6–6 bicyclic fragment was developed. The 6–6 ring fragment and the five-membered ring fragment were unified via a metal-halogen exchange/intermolecular addition reaction. Subsequently, the central 6–5 bicyclic ring system was constructed through a Michael/aldol cascade. The successful establishment of these strategic transformations allowed for an efficient and rapid construction of spiroannulated 6–6–6–5–5 pentacarbocyclic core via a convergent manner. Finally, the total syntheses of naturally occurring (+)-chamaecydin and (+)-isochamaecydin and their corresponding 1’,5’-stereoisomers have been achieved divergently by appropriately orchestrating the reaction sequence including isopropyl incorporation, oxidation state adjustment, and carbonyl group-directed regio- and stereoselective cyclopropanation at a late stage.

gem-Hydrogenation and gem-hydroboration of alkynes are highly unorthodox transformations, but asymmetric such gem-addition reactions are unprecedented. They have now been achieved with excellent levels of regio- and stereoselectivity using ynamides carrying an Evans oxazolidinone as the substrates. The resulting pianostool ruthenium carbenes were fully characterized and could even be engaged in catalytic downstream reactions.

Abstract

Ynamides, when reacted with H₂ or HBpin in the presence of [Cp*RuCl]₄, convert into chiral-at-metal Fischer carbenes by regioselective gem-hydrogenation or gem-hydroboration of the polarized triple bond, respectively. gem-Hydroboration concomitantly affords a carbogenic borylated stereocenter adjacent to the ruthenium carbene unit, the configuration of which can be controlled using an Evans auxiliary. These are the first examples of asymmetric gem-addition reactions to alkynes known in the literature; representative pianostool ruthenium carbene complexes formed by this unconventional route were characterized by crystallographic and spectroscopic means. They undergo various stoichiometric reactions and can even entertain catalytic asymmetric transformations, such as hydrogenative cyclopropanations or a novel type of borylative cycloisomerization.