Finn Moeller

Nature Chemistry, Published online: 11 March 2025; doi:10.1038/s41557-024-01729-0

Transfer hydrogenation is challenging to apply to aryl halide reductive cross-couplings because of competing hydrogenolysis. Now aryl halide cross-couplings mediated by sodium formate have been developed. These processes display orthogonality to Suzuki and Buchwald–Hartwig couplings as pinacol boronates and anilines are tolerated and, owing to chelated intermediates, effective for challenging 2-pyridyl systems.

An electrochemical three-component synthesis of alkyl alkenesulfonates from cinnamic acids, SO₂, and alkyl alcohols is reported. This metal-free process employs inexpensive and readily available graphite electrodes in combination with easy-to-use stock solutions of SO₂ and enables a straightforward decarboxylative preparation of styrene sulfonates via a pseudo-Kolbe type pathway.

A novel, electrochemical three-component reaction for the synthesis of alkyl alkenesulfonates from cinnamic acids, SO₂, and alkyl alcohols is reported. This metal-free process employs inexpensive and readily available graphite electrodes in combination with easy-to-use stock solutions of SO₂ and enables a straightforward construction of the styrene sulfonate scaffold via a decarboxylative transformation. Mechanistic studies indicate a pseudo-Kolbe type reaction. This novel reaction pathway enables a regioselective synthesis of alkenesulfonates from substituted cinnamic acids without double-bond translocation. Gram-scale and anolyte reusability experiments demonstrate the applicability of this process for the construction of alkenesulfonates from cinnamic acids as potential biogenic feedstock.

Nature, Published online: 11 March 2025; doi:10.1038/d41586-025-00729-5

Experts weigh in on the risks of moderate drinking — and how people should assess them.

The facile preparation of alkenyl sulfoximines, monoaza analogues of sulfones, by condensation of alkyl sulfoximines with aldehydes and their palladium-catalyzed Suzuki–Miyaura cross-coupling are reported. These alkenyl electrophiles underwent unique oxidative addition of the C−S bond to Pd to provide alkenes with three substituents. DFT calculations revealed the crucial role of the boronic acid in the transformation.

Abstract

Although numerous transition-metal catalyzed cross-coupling reactions of alkenyl electrophiles with a sulfur(VI) leaving group, mainly alkenyl sulfones, have been developed, most rely heavily on highly nucleophilic Grignard reagents, and the use of organoboron reagents remains challenging. We report herein facile preparation and the following Pd-catalyzed Suzuki–Miyaura cross-coupling reaction of alkenyl sulfoximine, a monoaza analog of sulfone. The condensation of alkyl sulfoximine with aldehydes, developed in this study, makes alkenyl sulfoximines more readily available. The resulting alkenes undergo an unprecedented oxidative addition of the C−S bond to the Pd center. This cross-coupling proceeds with retention of its original stereochemistry and provided alkenes bearing three different functionalities in a stereoselective fashion. DFT calculations highlight the critical role of boronic acid and in situ-generated boroxines in facilitating this transformation.

Science, Volume 387, Issue 6738, Page 1108-1114, March 2025.

This review aims to summarize pioneering studies and recent discoveries in organic electrosynthesis associated with sulfonium salts. The comprehensive literature survey provides aspects of how chemists benefit from electrochemistry and encourages further developments in this direction.

Abstract

Sulfonium salts are typically bench-stable and readily available reagents that showcase diverse chemical reactivities. Owing to these synthetically valuable features, sulfonium salt chemistry has witnessed considerable momentum over the past decades. Particularly, the merger of sulfonium reagents and electrosynthesis enabled the utilization of electric current in place of cost-intensive and hazardous chemical redox agents to maximize the attractive characteristics of sulfonium salts. Additionally, electrochemistry has allowed chemists to dial in the desired redox potential, offering selective access to target products that are otherwise unattainable by either thermal or photochemical manifolds. These advantages of electrochemistry led to major advances in sulfonium salt chemistry. Thus, we, herein, provide an overview of early pioneering findings and recent progress devoted to organic electrosynthesis associated with sulfonium salts until December 2024, aiming to stimulate future progress in this rapidly evolving arena.

Nature, Published online: 05 March 2025; doi:10.1038/d41586-025-00187-z

Potato genomes that contain the complete sequences from both sets of chromosomes uncover the deleterious variations previously hidden in genomes disclosed for only one set of chromosomes. An ideal set of genes was designed computationally by combining desirable sequences from different potato varieties. This ideal genotype could guide the breeding of hybrid potatoes.

Nature, Published online: 04 March 2025; doi:10.1038/d41586-025-00521-5

Vukosi Marivate learnt that communities, not just superstar individuals, can open doors in artificial intelligence.

The combination of Lewis bases and hydrosilanes has recently emerged as a mechanistically diverse manifold to facilitate various defunctionalizations, silylations, and intramolecular rearrangements. This article presents the first example applying this remarkable reagent combination towards intermolecular C−C bond formation. A transition metal-free hydroalkylation reaction is described, alongside mechanistic experiments that support a plausible pathway wherein the silane acts as both an H atom and electron donor, enabling the synthesis of highly reactive carbanions via reductive radical polar crossover.

Abstract

Hydrosilanes and Lewis bases are known to promote various reductive defunctionalizations, rearrangements, and silylation reactions, facilitated by enigmatic silicon/Lewis base-derived reactive intermediates. Despite the wide variety of transformations enabled by this reagent combination, no examples of intermolecular C(sp³)−C(sp³) forming reactions have been reported. In this work, we've identified 1,1,3,3-tetramethyldisiloxane (TMDSO) and KO^tBu as a unique reagent combination capable of generating benzylic nucleophiles in situ from styrene derivatives, which can subsequently react with alkyl halides to give a new C(sp³)−C(sp³) linkage via formal hydroalkylation. Mechanistic experiments suggest that the reaction proceeds through a key hydrogen atom transfer (HAT) step from a hydrosilane reducing agent to styrene, affording a benzylic radical that undergoes reductive radical polar crossover (RRPC) and subsequent S_N2 alkylation.

The one-electron oxidation of alkynylferrates(III) enables the synthesis of the corresponding high-valent Fe(IV) alkynylides. These organoiron complexes have been characterized by single crystal X-ray diffraction analysis, EPR, NMR, ⁵⁷Fe Mössbauer, X-Ray absorption (XAS) and emission (XES) spectroscopies and theoretical calculations (DFT and CASSCF). The isolated Fe(IV) alkynylide complexes react at room temperature to form 1,3-diynes.

Abstract

The isolation of thermally unstable and highly reactive organoiron(IV) complexes is a challenge for synthetic chemists. In particular, the number of examples where the C-based ligand is not part of the chelating ligand remains scarce. These compounds are of interest because they could pave the way to designing catalytic cycles of bond forming reactions proceeding via organoiron(IV) intermediates. Herein, we report the synthesis and characterization, including single-crystal X-ray diffraction, of a family of alkynylferrates(III) and Fe(IV) alkynylide complexes. The alkynylferrates(III) are formed by transmetalation of the Fe(III) precursor [(N₃N’)Fe^III] (N₃N’³⁻ is tris(N-tert-butyldimethylsilyl-2-amidoethyl)amine) with lithium alkynylides, and their further one-electron oxidation enables the synthesis of the corresponding Fe(IV) alkynylides. The electronic structure of this family of organometallic Fe(III) and Fe(IV) complexes has been thoroughly investigated by spectroscopic methods (EPR, NMR, ⁵⁷Fe Mössbauer, X-Ray absorption (XAS) and emission (XES) spectroscopies) and theoretical calculations. While alkynylferrates(III) are sluggish to engage into C−C bond forming processes, the Fe(IV) alkynylides react to afford 1,3-diynes at room temperature. A bimolecular reductive elimination from a bimetallic Fe(IV) intermediate to form the 1,3-diynes is proposed based on the mechanistic investigations performed.

Electrochemical amino-oxygenation of alkene radical cations with bisnucleophiles enabled the formation of saturated N/O-heterocycles. In situ EC-MS data offered valuable insights into the radical cation-initiated difunctionalization, allowing precise control over regio- and chemoselectivity.

Abstract

Regioselective functionalization of alkenes to create nitrogen- and oxygen-containing heterocycles remains a significant challenge in organic synthesis. Because of their unique electronic and biological properties, these heterocycles are crucial in pharmaceuticals and materials. Herein, we present an electrochemical amino-oxygenation of alkenes using alkene radical cations and bisnucleophiles, enabling the synthesis of saturated N/O-heterocycles in an undivided cell. This method employs readily available amides and alkenes, eliminating the need for additional oxidants or redox catalysts. The in situ generation of alkene radical cations results in high yields with excellent regio- and chemoselectivity. Our approach offers a direct route to six-, seven-, and eight-membered N/O-heterocycles from simple starting materials, broadening access to complex molecules essential for medicinal chemistry and materials science.

Preparation of renewable terephthalates and aromatic diisocyanates is presented using a transition metal-free route through a mild electrochemical decarboxylative aromatization on gram scale. Terephthalates were readily converted into aromatic diisocyanates in flow and used to synthesize 100 % renewable thermoplastic polyurethanes.

Abstract

Aromatic diisocyanates, invaluable commodity chemicals for polymer manufacturing, are produced annually on megaton scales from petroleum-derived diamines via phosgenation. Existing routes toward renewable alternatives are sparse and limited by access to functionalized aromatic starting materials, such as terephthalates. Herein, we report the development of a robust route to renewable terephthalates and aromatic diisocyanates from D-galactose via Eastwood olefination and Diels–Alder cycloaddition, followed by a mild electrochemical decarboxylative aromatization. This process was developed and applied on gram-scale to synthesize terephthalates, which were transformed into aromatic diisocyanates via Curtius rearrangement in flow. We demonstrate gram-scale preparation of 1,4-phenylene diisocyanate and 2,5-toluene diisocyanate and formulation of these monomers to prepare fully renewable thermoplastic polyurethanes. Preparation of these renewable aromatic diisocyanates proceeds without the use of high-pressure gases or costly transition-metals and represents a novel route to fully renewable aromatic diisocyanates.

Herein, anodic borohydride oxidation is demonstrated to have great potential for successfully replacing sacrificial metal anodes in a variety of electroreductive organic transformations. This anodic counter reaction effectively serves as the inverse of cathodic proton reduction, producing H₂ at inert carbon-based electrode materials.

Abstract

An efficient reaction at the counter electrode is of key importance for the success of net oxidative and net reductive electrochemical transformations. For electrooxidative processes, cathodic proton reduction to H₂ serves as the benchmark counter reaction. In contrast, net reductive electrochemical transformations have less attractive oxidative counter reactions to choose from and commonly rely on dissolution of a sacrificial anode that effectively results in stoichiometric metal consumption for the processes. In this study, we demonstrate that anodic borohydride oxidation has great potential to successfully replace the use of such sacrificial anodes for a variety of electroreductive organic transformations. This anodic transformation effectively serves as the inverse of cathodic proton reduction, producing H₂ using inert carbon-based electrode materials.