Tomas Horsten

Nature Synthesis, Published online: 27 November 2024; doi:10.1038/s44160-024-00701-7

Electrochemical fragmentation for alkene difunctionalization

Electrochemical hydrogenation of furfural on Pd/C catalysts under acidic conditions is investigated. Electrochemistry coupled with mass spectrometry and HPLC is used to analyze the reaction products and Tafel analysis gives insight into the reaction mechanism. The study investigates the influence of the applied potential on the Faradaic efficiency and highlights the blocking effect of furfuryl alcohol on the reaction.

Abstract

In this work, we present an insight into the mechanism of electrochemical hydrogenation of furfural on carbon supported palladium nanoparticles. By directly coupling electrochemistry with mass spectrometry, we were able to, for the first time, deconvolute the hydrogen evolution reaction and electrochemical hydrogenation by measuring the mass signal for hydrogen and 2-methylfuran. This approach also allowed us to extract the Tafel slopes for each reaction and get insights into mechanisms. The results indicate that the hydrogenation occurs by a Langmuir–Hinshelwood type process rather than by proton-coupled electron transfer. Further findings recognize the blocking character of furfuryl alcohol (FA) where the latter or one of its intermediates blocks the electrochemical hydrogenation. Additionally, FA is shown to be a precursor for 2-methyl furan formation. Accordingly, specific guidelines towards improvement of reaction performance are suggested.

A light-powered molecular motor featuring a specifically engineered helicene moiety is presented. The inversion of the helicene fragment is mechanically coupled to the unidirectional rotation of the motor in a 6-step rotation cycle, which involves 8 isomers. This coupled motion results in the dynamic modulation of the handedness of the helicene by the motor via a central to helical to helical chiral transmission mechanism.

Abstract

Towards complex coupled molecular motions, the remote handedness inversion of a helicene moiety was achieved by a rotary molecular motor. The use of a specifically engineered dynamic helicene stator in a novel overcrowded-alkene second-generation molecular motor based on a fluorinated dibenzofluorene fragment allows for an unprecedented control over helicity inversion. This is achieved by the mechanical coupling of the rotation of the rotor to the helicene inversion of the stator half via a remote chirality transmission process. Thus, the unidirectional rotary motion generated upon irradiation is used to invert the dynamic stereochemistry of a helicene, leading to a 6-step cycle with eight intermediates. In this cycle, both alternation between P and M configurations of the helicene stator and dynamic thermal interconversion (paddling motion) can be achieved. In-depth computational and spectroscopic studies were performed to support the associated mechanism. The control over coupled motion and dynamic helicity offers prospects for the development of complex responsive systems.

This article discusses the use of CoSalen as an immobilized electrocatalyst in electrosynthesis. It explores various applications of these catalysts and presents immobilization strategies for different molecular catalysts. The article also examines the use of other immobilized electrocatalysts in synthetic organic electrochemistry, aiming to shed light on their possible applications in organic electrosynthetic processes.

Abstract

There have been significant advancements in the electrosynthesis of fuels and organic molecules, making it an increasingly sustainable and cost-effective alternative to traditional chemical redox reagents. Early versions of these systems faced challenges in chemoselectivity due to high applied overpotentials, which have been mitigated with the introduction of molecular electrocatalysts, like metal salens (MSalens). These MSalens reduce the required overpotentials, increase turnover numbers (TON), and have simple modularity within their ligand structure allowing for tunable selectivity. While these MSalen electrocatalysts are typically used homogeneously for engineering simplicity, downstream separations are often costly and time-consuming. Immobilization of MSalens addresses these issues by enabling synthesis at lower potentials, achieving high selectivity, and facilitating straightforward separations. This review explores the application of MSalens in electrosynthesis and immobilized molecular electrocatalysts in organic electrosynthesis.

The combination of a site-selective thianthrenation with a Catellani reaction provides access to 3,5-dimethylated arenes. The developed reaction is complementary to the previously discovered reductive ipso-alkylation of aryl thianthrenium salts and extends the possibilities for late-stage methylation of arenes with a single aryl thianthrenium salt.

Abstract

Here we report the reaction of aryl thianthrenium salts that allows selective functionalization of the meta position of arenes. The combination of a site-selective thianthrenation with a Catellani reaction provides access to 3,5-dimethylated arenes. The developed reaction is complementary to the previously discovered reductive ipso-alkylation of aryl thianthrenium salts and extends the possibilities for late-stage methylation of arenes with a single aryl thianthrenium salt.

Publication date: 1 December 2024

Source: Chemical Engineering Journal, Volume 501

Author(s): Stefan Desimpel, Jan Dijkmans, Koen P.L. Kuijpers, Matthieu Dorbec, Kevin M. Van Geem, Christian V. Stevens

Nature, Published online: 13 November 2024; doi:10.1038/s41586-024-08342-8

Photochemical permutation of thiazoles, isothiazoles and other azoles

Nature, Published online: 12 November 2024; doi:10.1038/d41586-024-03704-8

Worryingly high prevalence of retraction among top-cited researchers

Synlett
DOI: 10.1055/a-2442-1796

Spirocyclobutanes have gained significant attention in medicinal chemistry discovery programs due to their broad spectrum of biological activities and clinical applications. Utilizing ring strain in small molecules to drive organic transformations is one of the most powerful tools in chemical synthesis. Our research group has focused on developing new synthetic strategies enabled by ring strain to construct complex molecules selectively and efficiently. This account summarizes our recent efforts toward the synthesis of a library of functionalized spirocyclobutanes by harnessing the ring strain of bicyclo[1.1.0]butanes. Three spicrocyclization cascades have been developed to incorporate a diverse range of radical precursors into spirocycobutanes.1 Introduction2 Synthesis of Spirocyclobutyl Lactones and -Lactams using Bifunctional Reagents3 Dual Photoredox/Nickel Catalysis for the Synthesis of Spirocyclobutyl Lactams4 Synthesis of Spirocyclobutyl Oxindoles under Photoredox Catalysis5 DFT Studies6 Conclusion
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Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

An efficient electrocatalytic hydrogenation strategy for the conversion of unsaturated C−N bonds to amines is investigated with vacancy-rich Cu₃P nanowires electrode in aqueous solution under mild conditions. Over 99 % yields of amines are achieved us a series of aromatic nitriles, heterocyclic nitriles, aliphatic nitriles, and imines as reactants.

Abstract

Renewable energy driven electrochemically hydrogenation of unsaturated C−N bonds with water as a hydrogen source provides an eco-friendly route for amine production. However, the potential commercial applications of this strategy were limited by the lack of relevant extended research. Here we demonstrate an efficient electrochemical hydrogenation system for the formation of amines from nitriles by a vacancy-rich copper phosphide catalyst. The catalytic system achieves a yield of 99 % and a Faraday efficiency of 99 % for the hydrogenation of benzonitrile. Mechanism study shows that benzonitrile is spontaneously adsorbed on the electrode surface and the electrogenerated active adsorbed hydrogen is the key reactive intermediate for hydrogenation. Theoretical calculation results show that vacancy-induced active sites chemisorb the N atom, thus accelerating C≡N bond activation for hydrogenation. Encouragingly, good yields of amines (≥99 %) are obtained when benzonitrile is replaced by a series of aromatic nitriles, heterocyclic nitriles, aliphatic nitriles, and imines. These results show the general applicability of this method for the synthesis of various amines.

We report a catalytic deoxyamination of 2-arylethanols in hexafluoroisopropanol, which directly installs various amino groups, including sulfonamides, amides, ureas and anilines. The transformation relies on the intermediacy of a phenonium ion, whose formation was rationalized by mechanistic experiments and DFT calculations.

Abstract

The catalytic deoxyamination of readily available 2-arylethanols offers an appealing, simple, and straightforward means of accessing β-(hetero)arylethylamines of biological interest. Yet, it currently represents a great challenge to synthetic chemistry. In most cases, the alcohol has to be either pre-activated in situ or converted into a reactive carbonyl intermediate, limiting the substrate scope for some methods. Examples of direct dehydrative amination of 2-arylethanols are thus still scarce. Here, we describe a catalytic protocol based on the synergy of triflic acid and hexafluoroisopropanol, which enables the direct and stereospecific amination of a broad array of 2-arylethanols, and does not require any pre-activation of the alcohol. This approach yields high value-added products incorporating sulfonamide, amide, urea, and aniline functionalities. In addition, this approach was applied to the sulfidation of 2-arylethanols. Mechanistic experiments and DFT computations indicate the formation of phenonium ions as key intermediates in the reaction.

A series of intriguing transformations of alkynyl tetracoordinate boron compounds upon reaction with sulfur electrophiles are disclosed, in which substituted benzothiophenes, five/four-membered boracycles, and alkenyl sulfides are readily assembled under mild reaction conditions. These transformations feature novel reaction modes as well as unusual reaction mechanisms and provide valuable products with high efficiency.

Abstract

Zweifel reaction is a powerful strategy to construct olefins from alkenyl tetracoordinate borons in organoboron chemistry, however, it usually only involves one functional group migration and then undergoes an elimination process affording alkenes or alkynes exclusively. Herein, we disclose several intriguing interception of alkynyl tetracoordinate borons with sulfur electrophiles. Wherein, the substituted benzothiophenes are accessed by consecutive 1,2-migrations and intramolecular electrophilic substitution, meanwhile, the challenging and elusive five/four-membered boracycles are easily assembled, and an approach to alkenyl sulfides with good stereoselectivity was developed as well. Moreover, by adding readily available deuterium sources, the tetrasubstituted deuterated alkenyl sulfides with high deuteration rates are constructed. These protocols not only improve atom economy by prohibiting the elimination of Zweifel intermediate, but also enrich the reaction modes of alkynyl tetracoordinate borons achieving versatile value-added sulfur-containing molecules. Mechanistic investigations illustrate that dichlorosulfoxide (SOCl₂) and dialkylaminosulfur trifluoride-type reagents (DAST-type) as surfur sources could promote dual 1,2-aryl migration of alkynyl tetracoordinate borons, which are distinct from traditional Zweifel reaction, and the regulation of steric hindrance could also make four-membered boracycles and alkenyl sulfides feasible. And these transformations feature novel reaction modes and unusual reaction mechanisms with valuable products in high efficiency.

The ability to selectively edit organic molecules at the atomic level has the potential to streamline lead discovery and optimization in the pharmaceutical and agrochemical industry. While numerous atom insertion and deletion reactions have recently been reported, examples of single atom swaps remain scarce due to the challenge of orchestrating the selective cleavage and formation of multiple chemical bonds around the same atom. We herein report a method for the carbon-to-nitrogen atom swap in N-alkyl indoles, allowing for the direct conversion of indoles to the corresponding benzimidazoles. The reaction leverages the innate reactivity of the indole scaffold to engage in an initial oxidative cleavage step, followed by oxidative amination, Hofmann-type rearrangement and cyclization. This complex sequence of steps is mediated by the simple combination of commercially available PIDA and ammonium carbamate as nitrogen atom source. The reaction tolerates a wide range of functional groups which is demonstrated by the interconversion of 15 drug-like molecules implying its immediate applicability across a wide range of discovery programs. Furthermore, it shows how leveraging the innate reactivity of a common heterocycle can unlock otherwise challenging skeletal editing reactions.