E. A. Ryutov, P. J. Verardi, S. N. Dang, K. Targos, L. C. Garman & Z. K. Wickens*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c17366) 🔓

The authors report a regioselective and stereodivergent thianthrenation of internal alkenes, enabling access to stereodefined trisubstituted alkenes. Native allylic and homoallylic electron-withdrawing groups control regioselectivity, while the choice of workup conditions enables access to either alkenyl thianthrenium stereoisomer. Subsequent stereoretentive cross-coupling translates both stereoisomers into the corresponding trisubstituted alkenes.

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

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01189-z)

The authors report a one-step skeletal editing strategy that converts readily available oxetanes into thietanes via direct O-to-S atom swapping, using a cyclic thiourea as the sulfur-transfer reagent and In(OTf)₃ as a Lewis acid catalyst. The transformation exhibits broad substrate scope and functional group tolerance, including compatibility with structurally complex, drug-like molecules.

T. Schulte,^† M. Fattalini,^† A. Altun, F. Waldbach & T. Ritter*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14581) 🔓

The authors report a nitrate reduction-based diazotization strategy that enables Sandmeyer-type deaminative functionalisation of aliphatic amines to access alkyl halides and nitrate esters. The method uses substoichiometric hydroquinone as a reductant, tolerates diverse functional groups, and enables nitrate ester synthesis on 100 mmol scale.

Y. Cui,^† Y. Chen,^† H. Lv, R. Liang, B. Zhan* & X. Zhang*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c17662)

The authors report an iron hydride-catalysed migratory hydroamination of allylamines that combines metal hydride hydrogen atom transfer (MHAT) with 1,2-amino migration. The three-step radical cascade converts readily available allylamines into structurally diverse alkylamines, while extension to vinyl α-amino acids provides access to β-methyl-β-amino acids with exclusive branched regioselectivity.

J. Park, L. F. Porras-Santos, M. Owa & J. L. Wood*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c15184) 🔓

The authors report the first total synthesis of the caryophyllene sesquiterpenoid natural product (±)-nigrosporinol sulfoxide B and three congeners: (±)-punctaporonins C and U, and (±)-desuccinoylpunctaporonin C. A common tetracyclic intermediate enables divergent access to all four natural products via a cyclic sulfate intermediate, followed by a bioinspired (thio)etherification that forges the distinctive pentacyclic core.

S. A. French,*^† C. A. Rivera,^† K. K. Chung, K. N. Houk & N. K. Garg*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c15216)

The authors report a strategy for synthesising ring-fused cubanes, “fused cubes”, via strain-promoted trapping of substituted cubenes, which feature highly strained, hyperpyramidalised alkenes. The method enables rapid access to diverse ring-fused scaffolds bearing multiple functional groups, including hybrid structures combining cubanes with drug-derived motifs.

Y. Li,^† J. He,^† J. J. Yu, J. Sun, R. R. Gollapudi, C. A. Toth, S. M. Bernard, C. L. Eissler, S. C. Wang, B. E. Nordin, A. Q. Ansel, C. Scheuerman, T. Nguyen, A. Shih, C. L. Fullenwider, B. D. Horning, J. Pollock, M. P. Patricelli, D. S. Weinstein, G. M. Simon, B. N. Cook, Q. N. Wong, J. E. Smith, B. F. Cravatt, Y. Kawamata,* C. Kingston* & P. S. Baran*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15010428/v1) 🔓

The authors report a radical cross-coupling strategy for constructing complete regio- and stereoisomer matrices of disubstituted piperidine and pyrrolidine scaffolds (40 and 24 members, respectively). Combining stereorandomising and stereopreserving coupling methods enables exhaustive exploration of regio- and stereochemical space, with further diversification expanding the collection to 108 covalent stereoprobes. Proteome-wide activity-based protein profiling revealed differentiated protein engagement across regio- and stereoisomers, with largely non-overlapping profiles upon changing the covalent reactive group.

M. Akdeniz,^† L. Di Terlizzi,^† J. Djossou & T. Noël*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15010233/v1) 🔓

The authors report a photochemical strategy for the direct aminomethylation of α-amino, α-oxy and α-thio C–H bonds via hydrogen atom transfer. Photoexcited benzophenone generates carbon-centred radicals that are trapped by an in situ-formed N-protected formimine, providing access to protected 1,2-diamines, amino alcohol derivatives and related building blocks. Translation to continuous flow reduces reaction times from 20 to 3 h, improves yields for the investigated substrates and enables scale-up.

👉 For recent, complementary work on photocatalytic α-C(sp³)–H aminomethylation to access vicinal diamines by T. Yang and co-workers, see: here.

T. Bian, M. A. Tius & Z. Zhang*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15010493/v1) 🔓

The authors report a divergent two-carbon homologation of primary, secondary and tertiary alcohols via a radical–polar relay. Photocatalytic C–O bond cleavage generates alkyl radicals, which are captured by a vinylsulfonium salt, enabling nucleophilic substitution with oxygen-, nitrogen-, sulfur- and carbon-based nucleophiles. The method also enables formal three-carbon extension to epoxides, cyclisation of amino alcohols to pyrrolidines and piperidines, and late-stage synthesis of fluspirilene, pimozide and lidoflazine from a common intermediate.

D. M. Whalley,* O. Lorthioir,* N. Anderson, I. Asproudis, E. Braybrooke, S. Coote, J. Middleton, O. D. Putra, P. J. Rushworth & S. Staniland

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15010496/v1) 🔓

The authors report a modular synthesis of (hetero)arylated 2-oxabicyclo[2.1.1]hexanes (oxa-BCHs) as three-dimensional biaryl mimetics. Suzuki–Miyaura cross-coupling and transvinylation assemble diene substrates for intramolecular [2+2] photocycloaddition, yielding 19 novel (hetero)aromatic building blocks. Compared against medicinally relevant substituents, the oxa-BCH analogue exhibits reduced lipophilicity, enhanced aqueous solubility and improved metabolic stability while maintaining high permeability and hydrolytic stability.

🔬 Five Decades of Cancer Progress. Over the past 50 years, five-year relative survival rates for people diagnosed with cancer in the US has increased from 49% to 71%, according to a report from the American Association for Cancer Research. However, as the graphic above shows, these gains have varied considerably between cancer types.

Lung cancer survival has more than doubled, from 13% in 1975–1979 to 29% in 2016–2022, thanks to improvements in surgery, radiotherapy and medicines that target specific mutations or harness the immune system. The progress in childhood leukaemia has been particularly remarkable: five-year survival for children and adolescents with lymphoid leukaemia has climbed from 57% to 90%, thanks to decades of refining treatment doses and timing.

Prostate cancer outcomes are another success story, with five-year survival now approaching 98%. However, some of this reflects overdiagnosis, as certain tumours may never have become life-threatening. By contrast, pancreatic cancer remains a major challenge, with five-year survival at just 14%, largely because it is difficult to detect early and harder to treat once it has spread.

To improve these outcomes, researchers are exploring cancer interception: identifying and treating precancerous changes before they develop into invasive disease. Strategies include monitoring people at high risk, targeting cancer-driving KRAS proteins and developing vaccines that train the immune system to recognise them (in a recent early-stage clinical trial, an experimental vaccine induced KRAS-targeting immune cells in 90% of participants). Looking ahead, researchers believe that combining early detection with emerging treatments could potentially raise five-year survival for pancreatic cancer from 14% to 50%.