MRV

Nature, Published online: 22 June 2026; doi:10.1038/d41586-026-01954-2

Artificial intelligence’s ability to enrich science will depend not only on model capability, but also on whether researchers, reviewers and funders reward originality over speed.

CCS Chemistry, Ahead of Print.
The electrochemical C(sp3)–H/S–H coupling of thiols is an atom-economical approach to accessing thioethers but remains challenging due to competing thiol over-oxidation. Herein, we report a strategy that circumvents these limitations by employing a quinoline mediator to generate stabilized electrophilic fluoroalkoxyl intermediates, which undergo nucleophilic substitution with electron-rich thiols to form C(sp3)–S bonds efficiently. Replacing hexafluoroisopropanol with trifluoroethanol enables the activation of tertiary and allylic C–H bonds. This protocol accommodates a broad substrate scope across diverse C–H coupling partners and thiols. It demonstrates significant utility through successful scaling in continuous flow, late-stage functionalization of complex molecules, and concise synthesis of sulconazole. This strategy is further generalizable to other electron-rich nucleophiles, including dialkyl amines, providing an oxidant-free route to the formation of C(sp3)–C and C(sp3)–N bonds.

Nature Catalysis, Published online: 09 June 2026; doi:10.1038/s41929-026-01539-2

Direct hydrogen atom transfer (d-HAT) for C(sp3)–H functionalization classically relies on O-centred photocatalysts. Now, neutral N-centred acridine photocatalysts have been added to the toolbox, enabling mild, scalable d-HAT that is compatible with a broad substrate scope and transition metal catalysis.

Synthesis
DOI: 10.1055/a-2886-7288

Distonic radical cations are an underexplored class of reactive species in which the radical and cationic centers are spatially separated within the same molecule. Among them, the α-ammonio radical exhibits unique reactivity inaccessible to conventional neutral radicals. This short review summarizes the characteristic reactivity patterns of α-ammonio radicals, tracing their historical development and highlighting recent advances. Selected state-of-the-art examples demonstrate that these distonic radical cations are promising next-generation intermediates offering access to transformations beyond the reach of classical radical chemistry.
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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

Axial chirality was established in the synthesis of acyclic alkenes from readily available benzofurans by direct enantio- and Z-selective functionalization of a vinyl C–O bond in the presence of a chiral nickel catalyst. Mechanistic studies suggest that the enantiocontrol in the formation of these atropisomeric aryl alkenes is enabled by an unprecedented epimerization between diastereomeric six-membered (Z)-styryl-nickelacycle intermediates.

ABSTRACT

Catalytic asymmetric transformation of benzofuran derivatives has received significant attention owing to its capacity to prepare chiral molecules from readily available feedstocks. Herein, an unprecedented asymmetric cross-coupling of benzofuran derivatives is reported for the construction of axial chirality. Employing a chiral nickel catalyst, this approach is achieved through direct enantio- and Z-selective dearomative functionalization of the vinyl C─O bond, providing efficient access to valuable atropisomeric acyclic alkenes. A broad substrate scope is demonstrated under mild conditions. Moreover, experimental and theoretical mechanistic studies suggest that the stereochemical outcome is facilitated by a dynamic epimerization between diastereomeric six-membered (Z)-styryl-nickelacycle intermediates.

A nickel/phosphine-catalyzed reductive cross-electrophile coupling enables the unprecedented allylation of alkynyl halides with allylic acetates. This strategy successfully overcomes the long-standing limitations of conventional skipped enyne synthesis and delivers structurally diverse 1,4-enynes with excellent chemo-, regio-, and stereoselectivity.

ABSTRACT

We have developed a Ni-catalyzed cross-electrophile coupling (XEC) strategy that enables the efficient synthesis of diverse skipped enynes from readily accessible alkynyl halides and allylic acetates. This method exhibits broad substrate scope, accommodating a wide range of aliphatic and aromatic electrophiles, as well as complex natural product- and pharmaceutical-derived motifs, which remains a challenge using the current methods. Mechanistic experiments and DFT studies support a double oxidative addition pathway, wherein Ni⁰ preferentially undergoes oxidative addition with the alkynyl halide. To our knowledge, this work represents the first example of a TM-catalyzed reductive cross-coupling between two electrophiles for the preparation of skipped enynes. The process proceeds with excellent stereoselectivity and notable regioselectivity, offering a promising platform for future development of asymmetric skipped enynes synthesis.

Quaternary carbon stereocenters can be widely found in natural products, chiral pharmaceuticals, and functional materials, which stereocontrolled construction remains one of the most formidable challenges in asymmetric catalysis. Organic electrosynthesis, which uses electrons as traceless redox reagents, enables the precise generation and controlled conversion of highly reactive intermediates under mild conditions, thereby providing a green and efficient platform for the assembly of these congested stereocenters. This review highlights recent advances in the electrochemical asymmetric construction of quaternary stereocenters and offers a systematic overview of this rapidly emerging area. Organized according to substrate classes and reaction design principles, with mechanism/activation mode introduced as a secondary classification criterion, the discussion focuses on four major strategies based on sp²-hybridized prochiral substrates: functionalization of poly-substituted alkenes, transformation of prochiral enolates, nucleophilic addition to carbonyl compounds, and nucleophilic addition to imine derivatives. In addition, two distinctive approaches, namely indole dearomatization and electrochemical kinetic resolution, are summarized with emphasis on reaction mechanisms, modes of chiral induction, and substrate scope. The review further analyzes the key challenges that continue to limit this field, including catalyst development, expansion of reaction manifolds, and practical translation to large-scale synthesis. Finally, future directions and opportunities are discussed with the aim of promoting the broader application of asymmetric electrochemical synthesis in the preparation of complex chiral molecules and the development of chiral pharmaceuticals.

While amide functionalizations are confined to deoxygenative or deaminative pathways, a direct route to hydrocarbons has remained elusive. We now report the conversion of amides into alkenes using 9-borabicyclo[3.3.1]nonane (9-BBN) and a Cp₂ZrCl₂ precatalyst under mild conditions. This transformation bridges two fundamental functional groups, translating the versatility of amide retrosynthesis to the construction of alkenes.

ABSTRACT

Amide derivatizations are important and useful transformations in organic chemistry, owing to the ready accessibility of amides. However, reported methodologies to date have been limited to either deoxygenative or deaminative pathways; the direct, single-step conversion of amides into hydrocarbons has remained elusive. In this work, by employing 9-borabicyclo[3.3.1]nonane (9-BBN) as the reductant and Cp₂ZrCl₂ as a precatalyst, we demonstrate that amides can be efficiently converted to alkenes under simple and mild conditions, which represents the third mode of amide derivatization after deoxygenation and deamination. Mechanistic investigations reveal that 9-BBN is crucial for the tandem C─O and C─N cleavage. This transformation links the two fundamental functional groups such that the richness of amide retrosynthesis is applied to alkenes.

We reported a deoxygenative single-carbon atom transfer strategy that directly couples alkenes and aldehydes to access strained small carbocycles. This overall transformation is enabled by a designer iodomethylphosphonium reagent that unifies atom-transfer radical addition and a cyclizative Wittig reaction at a single carbon center.

ABSTRACT

Single-carbon atom transfer is an attractive approach to increasing molecular complexity through the concurrent formation of four new covalent bonds. Yet, the success of these methods depends largely on atomic carbon reagents that harness carbene reactivity, thereby constraining the repertoire of transformations attainable within this regime. Here, we report a deoxygenative single-carbon atom transfer strategy that directly couples alkenes and aldehydes to access substituted alkylidenecyclopropanes. The key enabling development is the identification of a novel iodomethylphosphonium reagent that orchestrates photocatalytic atom-transfer radical addition and cyclizative Wittig olefination at a single carbon center. Mechanistic studies reveal that the electronically tailored phosphonium motif endows the key radical intermediate with the desired polarity for carbon delivery and, at the same time, enhances the accessibility of phosphorus ylides en route to both ring closure and Wittig reaction. This operationally simple method provides a modular entry from two abundant starting materials to highly strained small carbocycles featuring four newly formed bonds.

Isotelluroureas allow for the use of alkynoates for asymmetric (4+2)-heterocycloadditions with different Michael acceptors.

Alk-2-ynoates are readily available starting materials which, in principle, can be utilized for cycloadditions in analogy to structurally similar allenoates. However, their significantly lower reactivity makes activation by established isothiourea and isoselenourea Lewis base catalysts difficult. Capitalizing on the higher nucleophilicity and basicity of our recently introduced class of isotellurourea catalysts we now succeeded in successfully employing alk-2-ynoates for asymmetric (4 + 2)-heterocycloadditions as well, resulting in even improved enantioselectivities as compared to the use of analogous allenoates. These results demonstrate the high potential of the highly reactive isotelluroureas for the catalytic activation of less reactive starting materials where established catalyst classes come to their limits.

Nature, Published online: 19 May 2026; doi:10.1038/d41586-026-01605-6

AI might jeopardize the uncertainty required in science

Nature, Published online: 19 May 2026; doi:10.1038/d41586-026-01557-x

Artificial intelligence is rapidly accelerating scientific output, but risks narrowing inquiry, weakening judgement and undermining how scientists are trained.

A halogen-engineered perylenediimide radical anion (PDI-Br₈ ^•‒) shows exceptional air stability (>18 months) and strong 200–800 nm absorption. Its delocalized radical enables reversible redox cycling and ∼2 ns excited-state lifetime, driving a three-photon Z-scheme that catalyzes ppm-level, stereoselective (E)-enenitrile formation.

ABSTRACT

Persistent radical ions capable of sequential photon harvesting have remained rare due to their inherent instability. Here we report a halogen-engineered perylenediimide radical anion (PDI-Br₈ ^•‒) that exhibits exceptional air stability (>18 months) while maintaining broad and intense absorption across the visible spectrum (200-800 nm). This electronically delocalized radical displays reversible two-electron redox cycling and an extended excited-state lifetime (∼2 ns), enabling a self-sustained, three-photon, double Z-scheme photocatalytic process. At ultralow (∼ 100 ppm) loading, PDI-Br₈ ^•‒ efficiently catalyzed the one-pot, stereoselective coupling of terminal alkynes, acrylonitrile, and bromotrihalomethanes (CBrX₃; X = Br, Cl, F) to afford (E)-enenitriles under ambient conditions. Bromine substitution might have stabilized the unpaired spin and mitigated charge recombination, transforming an otherwise transient radical into a photochemically robust catalyst. This work establishes a molecular blueprint for multi-photon radical photochemistry, unifying energy storage, charge transport, and synthetic reactivity within a single organic framework.

A catalytic network embedding a formal rearrangement enables the first catalytic enantioselective multicomponent reaction (MCR) of sulfur ylides. In the presence of a bulky chiral phosphoric acid, the reaction combines sulfoxonium ylides, aldehydes and thiols, and affords synthetically versatile β-hydroxy-α-sulfanyl carbonyl compounds in enantioenriched form.

ABSTRACT

Sulfur ylides have emerged as versatile carbenoids for catalytic enantioselective X–H insertion reactions (X = C, N, O, and S), while offering a better safety profile compared to traditional diazo-based metal carbene precursors. However, the realization of valuable multicomponent reactions (MCRs) with sulfur ylides has been so far out of reach. Here, we report the enantioselective MCR of sulfoxonium ylides, aldehydes, and thiols catalyzed by a chiral phosphoric acid. Departing from carbenoid reactivity, the reaction pathway entails two sequential but nonoverlapping catalytic cycles, where the assembly of the components is followed by a delayed stereodetermining rearrangement across the central C─C bond of the molecule. The organocatalytic MCR delivers β-hydroxy-α-sulfanyl carbonyl products as single anti-diastereoisomers and generally in high yields and enantioselectivities. These products cannot be readily accessed by other catalytic means and are synthetic linchpins to a variety of α-sulfanyl carbonyl compounds via stereospecific substitutions of their hydroxy group.

Photochemical activation of a constrained phosphine enables carbene capture, rearrangement, and selective P─C homolysis. This establishes a light-driven P(III)→P(V)→P(III) manifold with controlled radical generation.

ABSTRACT

Geometrically constrained phosphines have attracted significant attention for their ability to mediate reactions traditionally associated with transition metals. Here, we show that visible-light excitation unlocks new transition-metal-like reactivity in a well-studied ONO-pincer phosphine. Photochemical generation of α-siloxy carbenes enables rapid P─C bond formation, affording bicyclic phosphines with complete diastereocontrol. These phosphine intermediates readily engage with electrophiles to form air- and moisture-stable phosphoranes, which, upon subsequent irradiation, undergo selective P─C bond homolysis, releasing carbon-centered radicals while regenerating the initial phosphine framework. Time-resolved EPR spectroscopy and DFT calculations reveal that geometric constraint is crucial for accessing both carbene-insertion rearrangement and P─C bond homolysis pathways not observed with conventional phosphines. Together, these findings establish a rare light-driven phosphine → phosphorane →phosphine (P(III) → P(V) → P(III)) reactivity loop and demonstrate how structural constraint enables main-group centers to perform elementary steps analogous to transition metals.