Finn Moeller

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.

Nature Chemistry, Published online: 21 November 2024; doi:10.1038/s41557-024-01668-w

Saturated N-heterocycles are ubiquitous structures among natural products and biologically active compounds, but methods to edit the ring size of these substructures are scarce. Now the ring expansion of unactivated cyclic amines has been achieved via sequential Ru-catalysed C‒C bond formation, retro-aza-Michael addition and a lactamization process to construct synthetically challenging medium-sized azacycles.

Nature, Published online: 21 November 2024; doi:10.1038/d41586-024-03823-2

Cecilie Steenbuch Traberg worried that choosing to have children during her graduate studies might signal a lack of career dedication.

Nature, Published online: 20 November 2024; doi:10.1038/s41586-024-08195-1

A transition-metal-free platform enables the formation of challenging C(sp3)–C(sp3) bonds in organic compounds via single-electron transfer, facilitating the coupling of functionalized fragments and expanding possibilities for efficient organic synthesis and reaction design.

The discovery of a new reactivity mode for π-arene metal complexes to promote carbon group insertion is reported. The reaction uses ruthenium η⁶-arene complexes supported by a tripodal ligand with enolates derived from α-halo- or α-(tosyloxy)esters to transform π-coordinated arenes to ring-expanded cycloheptatrienes in a single-step dearomatization process.

Abstract

Transition metal π-arene complexes enable the dearomatization of benzene rings to access diversified unsaturated carbocycles through multistep synthetic procedures involving sequential addition of nucleophiles and electrophiles. This work details a single-step dearomatization process by reaction of Ru(η⁶-arene) complexes with enolates derived from α-halo or α-(tosyloxy)esters to directly transform π-coordinated arenes to ring-expanded cycloheptatrienes.

We describe a cross-electrophile coupling of iminium ions with a range of electrophilic substrates to prepare tertiary amines. This reaction is mediated by the underexplored single-electron reducing power of the iodide counter anion, which is investigated both experimentally and through quantum chemical calculations.

Abstract

The reducing power of iodide anion is an underexplored property that can be used for the cross-electrophile coupling of organic molecules. Herein we harness this trait for the preparation of tertiary amines through the combination of two simple reagents: an electrophilic-carbon precursor and an iminium iodide in a dual role – both as nitrogen-containing building block and as reducing agent. The underlying mechanism of this new C−C bond-formation paradigm is explored through a combination of experiment and quantum chemical calculations.

Nature Communications, Published online: 19 November 2024; doi:10.1038/s41467-024-54379-8

Ciamician–Dennstedt rearrangement remains limited to halocarbene precursors. Herein, the authors report a general methodology for the Ciamician-Dennstedt reaction using α-halogen-free carbenes generated in situ from N-triftosylhydrazones.

Karl Ziegler is still known today for his outstanding achievements in chemical research, for which he was awarded the Nobel Prize in 1963. But who was the person behind this brilliant scientist? This article outlines Ziegler's biography. It describes his youth and study years in Marburg, his postdoctoral period and especially his role in the Nazi era.

Abstract

Karl Ziegler is considered one of the most outstanding chemists of the 20th century. In particular, his work on organometallic mixed catalysts, which allows the polymerization of ethylene at normal pressure, led to a revolution in plastics production and changed the everyday life of all mankind. In 1963, he was awarded the Nobel Prize in Chemistry for this work, together with Giulio Natta. This article focuses on Ziegler's early career, which has received little attention to date. It describes his youth and study years in Marburg, which partly coincide with the First World War. Subsequently, his postdoctoral period is examined, which led him via Marburg and Frankfurt to his first associate professorship in Heidelberg. Special attention is paid to his relationship to National Socialism, which he opposed. As a result, Ziegler experienced professional difficulties in the 1930s, such as repeated rejection when filling various professorships. His appointment as a full professor in Halle and his subsequent directorship at the Max-Planck-Institut für Kohlenforschung (Coal Research), where he finally achieved his greatest research achievement, are described in the following.

Nature, Published online: 13 November 2024; doi:10.1038/d41586-024-03671-0

Clinical trial in Malawi suggests that chewing gum sweetened with the natural compound xylitol is linked to a lower risk of preterm birth.

We present a groundbreaking electrochemical ring-opening protocol for the direct synthesis of remote amino alcohols via copper-catalyzed sequential paired electrolysis under mild, biocompatible conditions. This method enables rapid access to a wide variety of remote amino alcohols with diverse functional groups, utilizing an electro-redox ring-opening approach for efficient peptide alcohol modification and assembly. Mechanistic studies and DFT calculations confirm that water serves as both the solvent and hydrogen source, generating CuH to reduce aldehydes to alcohols.

Abstract

Amino alcohols, particularly remote amino alcohols and peptide alcohols, are valuable due to their functional diversity in biologically active compounds. However, traditional synthesis methods face significant challenges, making electrochemistry an attractive alternative. We have developed a mild and biocompatible sequential paired electrolysis strategy, leveraging copper-electrocatalysis to synthesize diverse remote amino alcohols, including unnatural peptide alcohols. Both experimental results and density functional theory (DFT) calculations demonstrated that water serves as both the hydroxyl source and the solvent, facilitating the generation of CuH with Cu(I) at the cathode, which in turn reduces the aldehyde intermediates formed during the reaction.

Nature Communications, Published online: 07 November 2024; doi:10.1038/s41467-024-54082-8

Although cyclopropanes are found in many natural products, agrochemicals, and pharmaceuticals, catalytic methods for cyclopropanation with two abundant substrates, mild conditions, high functional group tolerance, and broad scope are still highly desirable. Here, the authors report an intermolecular electrocatalytic cyclopropanation of alkenyl trifluoroborates with methylene compounds.

A concise, modular synthesis of the structurally novel natural product myxoquaterine-450 (1) has been accomplished. Four building blocks were assembled by cross-coupling reactions to establish the all-(E)-configured hexaene core. The C25,C26-diastereoisomer of 1 was prepared to clarify the absolute configuration of the yet unassigned stereogenic centers.

Abstract

Myxoquaterines represent a recently discovered class of natural products with intriguing biological properties. They were isolated from Pendulasporacea albinea MSr 11954 and display a unique structure combining heterocyclic (pyrrole, oxazoline), hexaene, and 2-amino-1,3-diol subunits. We have now synthesized the first example of a myxoquaterine natural product, myxoquaterine-450, in a highly convergent fashion, in which the sensitive hexaene unit was established in the final stages of the synthesis (16 linear steps starting from l-serine). Comparison of the synthetic material with an authentic sample allowed to establish and confirm the constitution and configuration of the natural product.

A highly efficient method for the C4-selective fluoroalkylation of pyridines was developed using readily available sulfinates and N-amidopyridinium salts. This photoinduced radical approach enables the difunctionalization of alkenes and [1.1.1]propellane, providing access to a wide variety of fluoroalkylated pyridines.

Abstract

Given the prevalence of pyridine motifs in FDA-approved drugs, selective fluoroalkylation of pyridines and quinolines is essential for preparing diverse bioisosteres. However, challenges are often faced with conventional Minisci reactions in achieving precise regioselectivity owing to competing reaction sites of pyridine and the limited availability of fluoroalkyl radical sources. Herein, we present a light-driven, C4-selective fluoroalkylation of azines utilizing N-aminopyridinium salts and readily available sulfinates. Our approach employs electron donor-acceptor complexes, achieving highly C4-selective fluoroalkylation under mild conditions without an external photocatalyst. This practical method not only enables the installation of CF₂H groups but also allows for the incorporation of CF₂-alkyl groups with diverse functional entities, surpassing the limitations of previous methods. The versatility of the radical pathway is further demonstrated through straightforward three-component reactions involving alkenes and [1.1.1]propellane. Detailed experimental and computational studies have elucidated the origins of regioselectivity, providing profound insights into the mechanistic aspects.

In this work, we proposed a strategy based on in vivo electrochemistry for early detecting high-altitude hypoxic brain injury (HHBI). The characteristic changes in the brain oxygen level under the high-altitude exposure directly associated with the brain hypoxia status. Given that brain hypoxia is the main pathogenesis of HHBI, the risk of HHBI can be prognosed 3 days in advance according to the characteristics of brain oxygen change within initial 1–2 hours of high-altitude exposure.

Abstract

High-altitude hypoxic brain injury (HHBI) is a kind of acute mountain sickness and the survival rate of patients with HHBI can be improved only if it is detected and treated at the early stage. However, limited by speediness and accuracy, it is still very difficult for most of current approaches to realize the early detection of HHBI. We propose herein a novel strategy for this goal based on spatiotemporal changes in the brain oxygen level. As revealed by in vivo electrochemistry, the characteristic changes of brain oxygen level under the high-altitude exposure are directly associated with the brain hypoxia status. Given brain hypoxia is the main pathogenesis of HHBI, the degree of HHBI can be diagnosed by the variation of brain oxygen, making the early detection of HHBI feasible. In addition, the risk of HHBI for mouse exposed to high-altitude hypoxia environments can be also prognosed days in advance.

We report herein a strategy for the homologation of alkenyl carbonyls via a sequence of cyclopropanation/light-mediated selective C−C cleavage. Depending on the substrate structure, intramolecular photoisomerization processes were favored or [3+2] annulations could be developed. Furthermore, a unified reductive strategy for the ring-opening of carbonyl cyclopropanes was achieved using diphenyl disulfide as a HAT reagent. These transformations open up new possibility for formal CH₂ insertion onto the α,β C−C bond of unsaturated carbonyl compounds, extending the current toolbox for the “skeletal editing” of aliphatic carbocycles.

Abstract

We report herein our studies on the direct photoactivation of carbonyl cyclopropanes to give biradical intermediates, leading to selective cleavage of the more substituted carbon-carbon bond. Depending on the substrate structure, extended alkenes were isolated or directly reacted in a photo-Nazarov process to give bicyclic products. Based on these results, a unified reductive ring-opening reaction was developed by using diphenyl disulfide as a hydrogen atom transfer (HAT) reagent. By performing a sequential cyclopropanation/selective ring opening reaction, we achieved a CH₂ insertion into the α,β bond of both acyclic and cyclic unsaturated carbonyl compounds. Our protocol provides a further tool for the modification of the carbon framework of organic compounds, complementing the recent progress in “skeletal editing”.