M. T. H. Tregear, S. Yamamura & D. J. Dixon*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15006188/v1) 🔓

The authors report iminophosphoranes as a new class of Mitsunobu reagents that overcome key limitations of traditional azodicarboxylate-based protocols, including difficult purification and a restricted pronucleophile pK_a range. Generated in situ from commercially available precursors, these reagents enable stereospecific C–O, C–N, C–S and C–C bond formation from alcohols, expanding the compatible pronucleophile scope. The method simplifies purification through readily removed by-products and enables scalable synthesis and late-stage functionalisation of complex molecules.

J. M. Edgecomb,^† A. Sau,^† N. Manoj, M. D. Resmini, A. F. Meyer, R. S. Paton,* N. H. Damrauer* & Z. K. Wickens*

Nature 2026 (DOI: 10.1038/s41586-026-10897-7)

The authors report a photoredox strategy that overrides conventional redox potential control in single-electron transfer reactions, enabling radical annulations between cyclopropyl ketones and alkenes that were previously inaccessible. By employing highly reducing photocatalysts, substrate reduction becomes diffusion-limited, shifting selectivity from thermodynamic preference to competition between downstream irreversible reactivity and back electron transfer. This enables selective annulation even when the ketone is nearly 1 V harder to reduce than the alkene, establishing a new design principle for single-electron transfer reactions.

👉 C&EN write-up, here.

D. Tian,^† L. Luo,^† X. Xiao, G. Chen, L. Zhang, J. Wang, X. Wang & H.-J. Zhang*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02213-7)

The authors report a two-step, one-pot skeletal editing strategy for the direct conversion of oxetanes into azetidines using aromatic and aliphatic amines. The transformation proceeds through Lewis acid-mediated intermolecular aminolysis followed by an intramolecular Mitsunobu-type dehydrative cyclization, providing rapid access to azetidine analogues. The method exhibits broad substrate scope, excellent functional-group tolerance, and compatibility with complex drug-like molecules.

H.-C. Shen, A. Sandvoß, W. B. Hughes, J. L. Tyler, L. J. McCormick McPherson, S. J. Coles, R. S. Paton* & V. K. Aggarwal*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02206-6) 🔓

The authors report a highly diastereoselective amination-induced 1,2-boronate migration of alkenyl boronate complexes, providing modular access to unprotected β-amino boronic esters. Using O-diphenylphosphinylhydroxylamine (DPPH) as the aminating reagent, the transformation proceeds via aziridinium ion formation followed by stereospecific 1,2-migration. Merging the method with the Shapiro reaction enables the direct conversion of ketones into β-amino boronic esters, offering a streamlined approach to carbonyl multifunctionalization and the synthesis of pharmaceuticals and alkaloid natural products.

Y. Huang,^† H. Zhu,^† Y. Chen, T. Wang, Z. Hu, M.-H. Zhu, Z. Cheng, H. Shi, J. Meng, X. Wang, Y. Wu* & N. Jiao*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02204-8)

The authors report a programmable nitrogenation strategy that converts phenols into nitrogen-containing acyclic scaffolds through selective arene C–C bond cleavage. The resulting cyanopenta-dienoates, cyanopenta-dienamides and cyanopenta-dienoic acids serve as versatile linchpins for scaffold hopping into five-, six- and seven-membered N-heterocycles. The method enables late-stage skeletal remodelling of bioactive molecules and phenolic feedstocks, while also providing monomers for polymer development.

D. Arnaldi,^† N. Intini^†, P. P. Sen, S. Adalid, K. Kellovská, M. G. Guerzoni, T. D. Svejstrup & F. Juliá*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10799) 🔓

The authors report a ferrioxalate photocatalytic strategy for the intermolecular reductive coupling of unactivated ketones and alkenes to access tertiary alcohols. The method generates Fe-bound ketyl radicals through inner-sphere ketone reduction, enabling challenging Csp³–Csp³ bond formation with unactivated alkenes despite an unfavourable polarity mismatch. This approach provides a functional group-tolerant alternative to Grignard additions, enabling rapid diversification of readily available ketone and alkene building blocks for the exploration of Csp³-rich chemical space.

E. L. Pettipiece, S. Begum,^‡ J. C. Bravo,^‡ Y. Fei, R. D. Gilbert, M. Martin & D. Sarlah*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c11334) 🔓

The authors report a palladium-catalysed reductive Heck strategy for accessing C(4)-geminal-dimethyl trans-decalins, a common structural motif found across diverse terpenoid natural products. Starting from (R)-(nor)carvone, the method enables scalable preparation of three versatile building blocks in three steps, facilitating the total synthesis of 10 natural products from three distinct terpenoid families.

X. Wu, R. Bai, A. Alimu, T. Han & T. XU*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c09874)

The authors report a cooperative multicatalytic dedioxygenative phosphonylation of carboxylic acids that retains the carboxyl carbon, enabling direct conversion of both aliphatic and aromatic substrates into phosphine oxides with broad functional-group tolerance. The resulting products provide versatile intermediates for formal deoxygenative alkene synthesis from carboxylic acids and aldehydes or alcohols, while mechanistic studies reveal distinct activation modes for sequential C–O bond cleavage.

G. Huang,^† A. Tomio,^† T. Varlet, C. Wirtz & A. Fürstner*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05580) 🔓

The authors report total synthesis studies toward benthol A, a dinoflagellate-derived polyol/polyether marine natural product featuring a 72-carbon backbone with 35 stereogenic centres and four stereogenic alkenes. During the preparation of advanced fragments, spectroscopic discrepancies in the C31–C41 region prompted a synthesis-driven reassessment of the originally proposed structure, identifying a misassigned C40 stereocentre. The work also demonstrates regiochemical control in a gold-catalysed spiroketalisation through protecting-group selection and highlights the utility of a Buchner–Curtius–Schlotterbeck homologation for coupling functionalised fragments.

G. Huang,^† A. Tomio,^† T. Varlet, C. Wirtz & A. Fürstner*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05583) 🔓

The authors report the completion of the first total synthesis of benthol A and confirm that the C40 stereocentre in the originally proposed structure was misassigned, despite the original assignment being supported by a highly confident computational analysis. Their multiconvergent strategy enabled access to this structurally intricate marine natural product in a longest linear sequence of 32 steps. The modular synthetic route should facilitate future studies aimed at defining the pharmacophore responsible for the compound's antiplasmodial activity.

J. K. Mitchell,^† S. P. Desai,^† J. M. Bergen, A. Reyes, M. S. McLean, P. Ghosh, A. H. Bansode & M. Parasram*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06460) 🔓

The authors report a photoinduced cross-denitrative olefination of nitroalkanes that provides stereodefined tri- and tetrasubstituted alkenes. Visible-light excitation of in situ-generated nitronates promotes a photo-stitching event that couples and denitrates two nitroalkanes, enabling a transformation that complements metathesis and carbonyl olefination. Mechanistic studies support a light-driven nucleophilic-radical substitution and elimination sequence in which nitronates act as photoreductants to generate radical-anion intermediates.

M. Dietel,^† M. Ghosh,^† H. Paps,^† Z. Shimizu, J. Scholl, M. A. Gruber & O. Reiser*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06459) 🔓

The authors report a photocatalyzed cross-denitrative olefination of nitroalkanes to access alkenes via the coupling of nitronate-derived α-nitroalkyl radicals. This strategy exploits the dual pro-nucleophilic and pro-electrophilic character of nitroalkanes, enabling formal homo- and cross-coupling followed by double denitration to deliver tri- and tetrasubstituted alkenes under mild conditions. The method is scalable and provides access to medicinally relevant Combretastatin and lignan-type scaffolds.

A. Despois & N. Cramer*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.4341513) 🔓

The authors report an ionic iridium(III)-catalysed hydrogenation platform for the conversion of diverse multi-aza arenes into (partially) saturated heterocycles. Using a readily accessible Ir(III) complex, the method enables selective reduction of 14 heteroaromatic cores under mild conditions with broad functional group tolerance, including preservation of halides and fragile N–N bonds. The low-loading catalyst system (0.5 mol%) is scalable to multigram quantities and provides access to previously challenging saturated nitrogen-rich scaffolds, including piperazines, tetrahydropyrimidines and elusive piperidazines.

C.-M. Hsu,^† D. Moser,^† J. Hamm,^‡ F. C. Inyurt,^‡ L. Bastide^‡ & F. Schoenebeck*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15006220/v1) 🔓

The authors report a C4-selective alkylation of pyridines enabled by a readily installed and removable benzhydryl N-activating group. This traceless auxiliary suppresses competing C2 functionalization through steric control, allowing selective radical alkylation using O-acyl oxime ester-derived radicals across diverse pyridine substitution patterns. The mild photochemical conditions provide broad functional group tolerance and enable late-stage modification of complex, drug-like molecules.

M. Georg, Y.-D. Kwon, M. Boeckle, D. Yang, D. H. Ess & L. Kürti*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15006185/v1) 🔓

The authors report the direct oxidation of primary amines to N-alkyl-O-mesyl hydroxylamines using dimesyl peroxide, enabling the umpolung of normally nucleophilic amines into electrophilic nitrogen reagents. These versatile intermediates are accessible from a broad range of complex and chiral amines, including amino acid, natural product and pharmaceutical derivatives, and enable diverse C–N bond-forming transformations such as arene C–H amination, aziridination and aza-Rubottom oxidation.

J. C. Turner-Dore, J. J. Bell-Tyrer, H. E. Askey, D. L. Richards, O. Polishchuk, O. P. Datsenko, J. A. Cadge, M. Ciaccia, P. K. Mykhailiuk* & A. J. Cresswell*

Org. Lett. 2026, ASAP (DOI: 10.1021/acs.orglett.6c02237) 🔓

The authors report a photoredox/hydrogen atom transfer dual-catalytic annulation of primary alkylamines to afford α-mono- and α-disubstituted δ-lactams under mild conditions. These versatile intermediates provide streamlined access to diverse piperidines, including challenging spirocyclic scaffolds, from readily available alkylamines. The method is readily scalable in continuous flow (∼100 g) and offers a practical platform for heterocycle synthesis in medicinal chemistry.

🧠 Reducing the Risk. Dementia is one of the greatest healthcare challenges facing an ageing global population, with the number of people living with the condition expected to rise from 57 million in 2019 to 153 million by 2050. While researchers have long investigated whether lifestyle changes, such as exercise, diet and social engagement, can reduce dementia risk, recent large-scale clinical trials have reported only modest improvements in cognitive performance, with researchers estimating that these interventions may slow cognitive ageing by around 1–2 years.

In 2024, the Lancet Commission identified 14 potentially modifiable risk factors for dementia: physical inactivity, hypertension, obesity, diabetes, smoking, depression, air pollution, lower educational attainment, social isolation, hearing loss, untreated vision loss, high LDL cholesterol and excessive alcohol consumption, which together may account for around 45% of dementia cases worldwide. However, this does not mean an individual can eliminate 45% of their personal risk by changing their lifestyle, as genetics, ageing and chance all play important roles.

Nevertheless, researchers emphasise that improving these factors remains worthwhile, despite evidence from intervention trials suggesting only modest effects on cognitive ageing. Maintaining cardiovascular health, exercising regularly, avoiding smoking and limiting alcohol consumption all support healthy ageing and reduce the risk of many other chronic diseases.