Finn Moeller

NHC-catalyzed umpolung of bicyclo[1.1.0]butane (BCB) aldehydes enables nucleophilic cycloaddition with carbonyls and imines to form bicyclic lactones and lactams. The resulting oxa- and aza-bicyclo[3.1.1]heptane products can be further transformed into valuable rigid 3D scaffolds, offering a simple and versatile approach to access new chemical space with potential applications in medicinal chemistry.

Abstract

Bicyclo[1.1.0]butane (BCB) has predominantly been explored as an electrophile or radical acceptor owing to its inherent polarity. However, its reactivity as a nucleophile remains largely unexplored. Herein, we report an umpolung strategy that reverses the innate polarity of bicyclobutane aldehydes via N-heterocyclic carbene (NHC) catalysis. This transformation enables the construction of novel rigidified lactones and lactams via coupling with diverse electrophilic partners, including aldehydes, ketones, and imines. The synthetic versatility of this method highlights its potential for applications in medicinal chemistry by providing new building blocks with defined exit vectors.

Nature, Published online: 26 August 2025; doi:10.1038/d41586-025-02636-1

A unified approach to access a variety of 1,n-dicarbonyls through a radical-promoted deconstructive process utilizing dual photocatalysis/carbene catalysis is reported. The utility of this strategy is demonstrated with a broad scope with robust functional group tolerance along with application in the preparation of γ-amino esters, three-component manifolds, and the first enantioselective deconstructive synthesis of 1,5-dicarbonyls using a chiral NHC catalyst.

Abstract

Dicarbonyl compounds are structural motifs that have been extensively utilized in synthetic chemistry, and their downstream transformations have proven valuable in synthesizing numerous heterocycles. Conventional methods for accessing such compounds include the Stetter reaction, the Michael reaction, and Friedel–Crafts acylation. However, a flexible and enabling platform for obtaining all types of 1,n-dicarbonyls remains undeveloped. Reported herein is a unified approach to access a variety of 1,n-dicarbonyls through a radical-promoted deconstructive process utilizing dual photocatalysis/carbene catalysis. The utility of this strategy is demonstrated with a broad scope with robust functional group tolerance along with application in the preparation of γ-amino esters, three-component manifolds, and the first enantioselective deconstructive synthesis of 1,5-dicarbonyls using a chiral NHC catalyst.

Nature Chemistry, Published online: 26 August 2025; doi:10.1038/s41557-025-01891-z

Nature, Published online: 21 August 2025; doi:10.1038/d41586-025-02547-1

An easily accessible and cheap iron complex is capable of catalyzing highly regio- and stereoselective trans-hydrostannation reactions of terminal alkyl alkynes as well as the stannylative cyclization of 1,6-enynes. The addition likely follows a “modified Chalk–Harrod” mechanism; the intervention of iron vinylidene intermediates can be excluded.

Abstract

The readily accessible iron complex [Cp*FeCl(tmeda)] is an effective catalyst for the highly regio- and stereoselective trans-hydrostannylation of terminal alkyl alkynes, affording a type of alkenylstannanes that is difficult to make otherwise. The R₃Sn- moiety is faithfully delivered to the terminal C-atom, unless a propargylic or homo-propargylic ─OH or ─NH₂ group is present in the substrate, which (partly or fully) inverts the regiochemical course; this steering effect, however, can be switched off upon protection of the protic site. The trans-addition likely starts by insertion of the [Cp*FeCl] fragment into the R₃Sn─H bond, followed by a migratory insertion of the ligated alkyne into the Fe─Sn unit of the Fe(IV) species thus formed. This “modified Chalk–Harrod” mechanism is manifested in a stannylative cyclization of 1,6-enyne derivatives, which has hardly any precedent either; a pathway via iron vinylidene intermediates can be excluded on the basis of deuterium labeling experiments.

RETRACTION: E. Santiago-Rivera and T. Scheibel, “Spider Eye Development Editing and Silk Fiber Engineering Using CRISPR-Cas,” Angewandte Chemie International Edition 64, no. 25 (2025): e202502068, https://doi.org/10.1002/anie.202502068.

The above article, published online on 13 April 2025 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Frank Maass; the German Chemical Society; and Wiley-VCH GmbH. In ongoing studies using CRISPR-Cas in spiders, the authors performed additional tests on the knock-out (KO) as well as knock-in (KI) mutants in correspondence with geneticists specializing in the use of CRISPR-Cas. The authors were unable to confirm that the KO as well as the KI occurred at the intended place in the genome. As the results in this study cannot be verified, the article must therefore be retracted.

Nature Communications, Published online: 19 August 2025; doi:10.1038/s41467-025-63052-7

Despite the abundance of oxygen-containing molecules, no unified approach exists that can activate various oxidation states of oxygenated functional groups for deoxygnenative functionalization. Here, we disclose a tandem, one-pot hydrosilylation–electroreduction sequence that enables the conversion of alcohols, aldehydes, ketones, and esters into nucleophilic reagents widely used in cross-coupling chemistry.

Abstract

Oxygen-containing functional groups are prevalent motifs in natural products and feedstock chemicals, but direct methods for their deoxygenative transformation remain rare due to the difficult cleavage of the strong C–O bond. Here, we develop a general activation strategy that employs hydrosilanes as activating reagents for alcohols, carbonyls, and esters to afford a common silyl ether intermediate. Electrochemical reduction of the in situ generated silyl ether results in C–O cleavage to afford a carbanion, which reacts with a number of electrophiles for the construction of C–Si, C–B, C–Ge, and C–Sn bonds.

Nature, Published online: 11 August 2025; doi:10.1038/s41586-025-09485-y

Reported herein is a practical and scalable electrochemical method for the oxidation of electron-deficient methylarenes to access aromatic aldehydes, eliminating the need for chemical oxidants or homogeneous transition-metal catalysts. This approach demonstrates exceptional performance under industrially viable conditions—high current densities, minimal electrolyte loading, and operation in an undivided cell without additives.

Abstract

Aromatic aldehydes are pivotal synthetic intermediates with applications in fine chemicals, pharmaceuticals, agrochemicals, and advanced materials. Although the oxidation of methylarenes represents an ideal route to aromatic aldehydes due to the availability of starting materials, existing methods face significant challenges, including reliance on hazardous oxidants, costly catalysts, poor scalability, and limited compatibility with electron-deficient substrates. To address these limitations, we report a practical and scalable electrochemical method for the oxidation of electron-deficient methylarenes to access aromatic aldehydes, eliminating the need for chemical oxidants or homogeneous transition-metal catalysts. This approach operates under industrially viable conditions—high current densities (75 mA cm⁻²), minimal electrolyte loading (0.05 equiv), and operation in an undivided cell without additives—to produce aromatic acetals, which are readily hydrolyzed to the corresponding aldehydes. The use of minimal electrolyte not only reduces costs and simplifies product isolation but also significantly enhances anodic oxidation selectivity, ensuring high efficiency and practicality. This protocol exhibits a broad substrate scope, compatibility with both batch and continuous flow systems, and exceptional scalability, as demonstrated by successful kilogram-scale synthesis.

“The most inspiring lecture I ever attended was part of a supramolecular chemistry course by the legendary François Diederich, where I first learnt about the mechanical bond… The most exciting thing about my research is that we not only get to make incredibly cool molecules like rotaxanes, catenanes and knots, but also think about how to use them to improve our lives…”

Find out more about Fredrik Schaufelberger in his Introducing… Profile.

Herein, electroreductive deoxysilylation of benzylic and allylic alcohols is demonstrated. The cathodic transformation proceeds via carbanionic intermediates and can be extended to aldehydes and ketones. Mechanistic studies reveal that the reaction outcome is dependent on the thermodynamics and kinetics for the coupling step in combination with the reductive stability of the coupling partner, thereby supporting a unified mechanism to that of deoxygenative cross-coupling with CO₂ as electrophile.

Abstract

Alcohols are highly common organic compounds but remain scarce as alkyl donors in synthetic procedures. Here, we describe an electrochemical procedure for their deoxygenative cross-electrophile coupling with hydrosilanes, furnishing organosilane products in good to excellent yields. Mechanistic studies provide insights into the operating pathways of this semi-paired electrolytic transformation, suggesting that silyl ethers are likely reaction intermediates. Furthermore, a unified mechanistic proposal is presented that accounts for observed reactivity differences with analogous deoxygenative electrocarboxylation.

The thioether-containing 6-methylthio-hexa-1,3-diene (MTHD) monomer is prepared from the biobased methional. The obtained isomeric cis-/trans-mixture of the diene can be successfully homo- and copolymerized via anionic techniques. Targeting the thioether groups via post-polymerization modifications (i.e. alkoxylation and alkylation) permits tailoring of the properties, for example for antimicrobial materials.

Abstract

Anionic polymerization of 1,3-dienes is a highly established approach for the synthesis of synthetic rubber and plays a key role for thermoplastic elastomers like poly(styrene-b-butadiene-b-styrene) (SBS). Aiming at novel concepts for tailoring the property profile of synthetic rubber in post-polymerization reactions, we introduce the thioether-containing 6-methylthio-hexa-1,3-diene (MTHD) as a diene monomer derived from the biobased methional. The obtained isomeric cis-/trans-mixture was successfully polymerized via anionic techniques. In situ ¹H nuclear magnetic resonance (NMR) kinetics revealed different reactivities of the trans- and cis-isomer and dispersities of Ɖ = 1.21–1.35. Copolymerization with isoprene afforded a series of well-defined statistical copolymers with molar masses up to 50 kg mol⁻¹, permitting precise adjustment of MTHD content from 2% to 10%. These copolymers exhibited moderate to narrow distributions (Ɖ < 1.19). Targeting the thioether groups via post-polymerization modifications (i.e., alkoxylation and alkylation) permitted tailoring of the properties of the diene-based copolymers. The respective sulfoxide was obtained selectively by mild oxidation and represents an internal antioxidant group. Introduction and testing of sulfonium functional polyisoprenes regarding their inhibition of the growth of gram-negative and gram-positive bacteria strains showed significant antimicrobial performance of the copolymers against Escherichia coli and Staphylococcus aureus.