A. J. Bracken,^† A. P. Lawrie,^† I. F. Romita & M. D. Levin*

Nature 2026 (DOI: 10.1038/s41586-026-10933-6)

The authors report an O-to-C skeletal editing of isoxazoles to pyrroles via N-propargylic enaminone intermediates. The one-pot, regioretentive strategy provides access to otherwise challenging pyrrole scaffolds by exploiting functionalisation patterns readily accessible in isoxazoles but difficult to achieve through conventional pyrrole synthesis. Mechanistic studies uncovered competing Conia–ene pathways and revealed a steric descriptor capable of predicting the reaction outcome.

J. D. Robinson,^† F. Richard,^† K. A. Ratkovich,^† J. M. Phelps & M. J. Gaunt*

Nature 2026 (DOI: 10.1038/s41586-026-11009-1)

The authors report a palladium-catalysed strategy for programmable remodelling of C–N bonds in tertiary benzylamines. N-Alkylation with bifunctional reagents generates quaternary ammonium intermediates that enable catalytic C–N bond disassembly and installation of new linkers between the aryl and amine fragments. The approach enables one-carbon homologation as well as insertion of aliphatic chains, oxygenated linkers, heterocycles and aryl groups, including late-stage editing of pharmaceutical scaffolds.

W. Choi, H. Ju,^‡ J. Park^‡ & S. Hong*

Nature 2026 (DOI: 10.1038/s41586-026-11006-4)

The authors report a skeletal editing strategy for positional isomerization of pyridines through nitrogen transposition. Sequential nitrogen insertion and extrusion reorganizes the pyridine core while preserving its substituents, enabling direct conversion of one isomer into another. The method accommodates mono-, di- and multi-substituted pyridines, and extends to complex drug scaffolds, including vismodegib, abiraterone acetate and etoricoxib.

J. J. Großkopf,^† J. Z. Wang,^† J. W. Gu, C. Bi, S. N. Dishman, X. Ma, Y.-h. Lam & D. W. C. MacMillan*

Nature 2026 (DOI: 10.1038/s41586-026-11043-z)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15003261/v1) 🔓

The authors report a radical-based strategy for the synthesis of sterically demanding dialkyl ethers enabled by a heteroatom homolytic substitution (het-S_H2) mechanism. Using carbon-centered radicals to overcome the steric limitations of classical polar substitution chemistry, a titanium-based catalytic platform combined with visible-light photoredox catalysis enables coupling of redox-active esters with alcohols across a broad range of substitution patterns. The method provides access to otherwise challenging dialkyl ethers, including BCP ether bioisosteres and enables late-stage diversification of complex pharmaceutical scaffolds.

L. Li,* F. Carpaneto, P.-P. Chen, K. N. Houk & V. H. Rawal*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02231-5) 🔓

The authors report that 9-bismatriptycene (BisTrip), a rigid, shackled form of triphenylbismuth, functions as a versatile aryl group transporter, enabling controlled and regiospecific α-arylation of diverse carbonyl compounds. BisTrip can be readily loaded with aryl groups from arylboronic acids in a one-pot procedure to give Aryl-BisTrip and is recovered in quantitative yield after aryl transfer to the carbonyl substrate. Notably, arylation of lithium enolates proceeds within seconds even at –78 °C and shows high stereochemical fidelity in a memory-of-chirality experiment.

W. Y. Tang,^† J. Guo,^† S. Nie, J. Yang, C.-L. Ji, X.-Z. Wang, H. Zhou, Y. Liu, X. Sun, M.-Y. Sun, Y. Zhang, D. Liu, Z. Li, J. Du, J. Yang & J. He*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02233-3)

The authors report heteroleptic copper(I)–BINAP complexes as triplet photosensitizers for cycloadditions of bicyclo[1.1.0]butanes with alkenes, providing access to multisubstituted bicyclo[2.1.1]hexanes. The catalysts’ extended excited-state lifetimes enable endergonic photosensitization for substrate activation, suppressing alkene polymerization and allowing the use of electron-deficient alkenes, enynes, dienes and aliphatic alkenes. The method also enables complementary synthesis of 2- and 3-aryl-substituted bicyclo[2.1.1]hexanes through activation of bicyclo[1.1.0]butanes or styrenes.

M. C. Lamb & T. H. Lambert*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c13866) 🔓

The authors report a metal-free C(sp³)–C(sp³) cross-coupling of primary amines via in situ diazene formation and visible-light-induced denitrogenation of unsymmetric diazenes. Central to this approach is the development of N-benzoyloxysulfamides, readily assembled from primary amines and bench-stable O-benzoylhydroxylamines, which undergo mild base-promoted conversion to diazenes followed by nitrogen extrusion using an inexpensive organic triplet sensitizer. The telescoped one-pot process tolerates diverse functional groups and enables late-stage modification of complex molecules.

L. M. Debie, T. Gotta, M. Turberg, N. Nöthling & B. List*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c12914) 🔓

The authors report an asymmetric organocatalytic benzylation and allylation of unactivated olefins using acetates as electrophiles. An imidodiphosphorimidate catalyst operating as a silylium Lewis acid enables enantioselective C–C bond formation across a range of olefins and acetate electrophiles. Mechanistic studies support an enantioconvergent S_N1 pathway featuring stereoablative ion-pair formation. The method provides a metal-free alternative to Tsuji–Trost-type allylations and enables access to enantioenriched odorants and pharmaceutical building blocks.

S. Sil, A. Mandal, B. Srinivasan, P. Datta, P. P. Dey, P. Mandal, S. Banerjee & S. K. Mandal*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05128)

The authors report an organometallic-free strategy for the methylation of aryl halides via generation of a methyl anion equivalent from methyl iodide. A two-electron-reduced phenalenyl catalyst enables this transition-metal-free cross-electrophile methylation across C–Br, C–Cl and even C–F bonds. The method provides broad access to methylated arenes and heteroarenes, including late-stage diversification of several drug molecules, while demonstrating the “Magic Methyl Effect” through enhanced activity of a methylated amoxapine analogue.

M. Pighetti, B. R. Miller, A. K. Ehrlacher, M. S. Sigman* & S. J. Miller*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10875)

The authors report an enantioselective aziridination of Z-disubstituted alkenes enabled by a dirhodium(II) metallopeptide catalyst featuring β-turn-biased peptidyl ligands. The method affords cis-aziridines in up to 99:1 e.r. with broad tolerance toward diverse aryl substitution patterns and functional groups. Data science-driven modelling compares enantioselectivity across the aziridination and a related C–H amination, revealing that catalyst sterics dominate enantioselectivity across both transformations.

L. Kong,^† J. Qin,^† H. Yu^† & T. Luo*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c13616)

The authors report a divergent strategy for the total synthesis of three Euphorbia diterpenoids, using a photochemical pyridinium ring contraction to construct highly functionalised cyclopentane cores. The resulting bicyclic aziridines undergo a series of skeletal rearrangements that enable the synthesis of (+)-resiniferatoxin, (−)-euphorstranoid B and (+)-pepluanol A. Notably, a rare cationic [3,4]-rearrangement provides the key step toward pepluanol A and suggests an alternative biosynthetic pathway for its formation.

E. R. Wearing, N. P. Kaushik, S. T. Hugie, M. S. Sigman* & A. G. Doyle*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c11233)

The authors report a comprehensive study of α- and β-scission selectivity in phosphoranyl radicals, combining experimental, computational and data-driven approaches to identify the factors controlling these competing pathways. The resulting insights enabled a photoredox-catalysed hydrosulfonylation of alkenes, with phosphine identity and reaction conditions controlling whether α- or β-scission occurs. The method provides access to hydrosulfonylation products in up to 64% yield and >50:1 selectivity, demonstrating switchable reactivity from the same starting materials.

P. Neigenfind, Y. Kawamata & P. S. Baran*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15007498/v1) 🔓

This Perspective examines redox-neutral radical cross-coupling using alkyl sulfonyl hydrazides, which serve as both radical sources and internal electron donors. By eliminating exogenous oxidants and reductants, this approach combines the operational simplicity of classical cross-coupling with the functional group tolerance of radical chemistry. The authors discuss the mechanistic foundations and emerging applications in synthesis and medicinal chemistry, while highlighting challenges toward developing these transformations into a general and predictive paradigm for bond construction.

P. Saha, F. J. A. Troyano, S. Ghosh & S. G. Newman*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15007587/v1) 🔓

The authors report a strategy for coupling transiently stable heterocyclic organolithiums through ultrafast Murahashi reactions. High-throughput experimentation identifies complementary catalyst systems that enable C–C bond formation on minute or subminute timescales, allowing sensitive organolithium species such as lithiated pyridines and quinolines to be coupled before decomposition. A continuous-flow “flash chemistry” protocol further extends the method to organolithiums that decompose on timescales of seconds.

E. T. Marris,^† A. D. Johnson-Sammy,^† B. D. Davis, D. J. Fowler, E. Casali, D. Uyghur, N. Onuska, J. Day, X. Li, G. Zanoni & J. M. Schomaker*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15007588/v1) 🔓

The authors introduce a modular “redox-release” platform that provides access to diverse S(VI) and fluoroalkyl radicals from a common proline-derived scaffold, decoupling radical identity from precursor activation. Oxidative or reductive activation converges on a shared α-amino radical intermediate, which undergoes β-scission to release the desired radical. The platform enables hydro(fluoro)sulfonylation, hydrofluoroalkylation and late-stage functionalisation, including the streamlined synthesis of medicinally relevant targets.

💉 From COVID to Cancer. A personalised mRNA vaccine for melanoma has reduced the risk of the cancer returning in a Phase III clinical trial. Developed by Moderna and Merck, intismeran uses the same mRNA technology as COVID-19 vaccines but is individually tailored to the mutations found in each patient's tumour. The trial enrolled 1,137 patients and combined intismeran with Merck's cancer immunotherapy Keytruda, significantly reducing the risk of both recurrence and the cancer spreading elsewhere. Earlier Phase II results had already shown a 49% reduction in the risk of recurrence or death, and a 59% reduction in the risk of distant metastasis or death.

The approach is remarkably individualised, with each patient's tumour sequenced to identify mutations that can produce cancer-specific proteins called neoantigens, which act as flags for the immune system. An mRNA vaccine is then designed to produce these targets in the body, training the immune system to recognise and attack the cancer. The vaccine can encode up to 34 neoantigens, meaning researchers are effectively designing a new vaccine for every patient. That's also a massive challenge: each vaccine can take months to produce and could be extremely expensive. However, mRNA offers an advantage here as the manufacturing process stays largely the same, even as the genetic sequence changes from patient to patient. Moderna's experience manufacturing billions of mRNA vaccine doses during the COVID-19 pandemic could therefore prove crucial.

The result is particularly impressive given the political headwinds facing mRNA technology in the US. Last year, the Department of Health and Human Services cancelled 22 mRNA vaccine projects worth nearly $500 million, while officials including Robert F. Kennedy Jr. repeatedly questioned the technology. It also makes for an ironic counterpoint to claims from the anti-vaccine movement that mRNA vaccines cause so-called “turbo cancer”. The backlash even affected the science directly, with investigators telling Nature that misinformation about mRNA vaccine safety made it harder to recruit patients at some US trial centres.

Meanwhile in the stock market, Moderna's $MRNA ( ▲ 8.86% ) shares surged 177% in a single day, from $63 to $174 — the largest one-day gain for an S&P 500 company in more than two decades. The jump added roughly $44.5 billion to Moderna's value, pushing it to $69.6 billion by the close.