A. J. Su, A. W. Chen, C. Li, N. R. Wierich, B. Wu, C. L. Phelps, T. J. Martínez & N. Z. Burns*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c15781)

The authors report a nitrogen deletion strategy for the conversion of secondary amides to ketones. The method proceeds via N-amination of the parent amide to form a hydrazide, followed by oxidation and loss of N₂ to furnish the ketone. This one-pot protocol uses simple commercial reagents in wet solvent under air, tolerates a broad range of functional groups and translates readily to gram scale.

S. Wang,^† D. A. Cagan,^† Y. Cao,^† B. P. Vokits, M. D. Palkowitz, Y. Kawamata, P. S. Baran* & K. M. Engle*

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01158-6)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2025-4sf42) 🔓

The authors report a Ni-catalysed directed C(sp²)–H alkylation of (hetero)arenes using alkyl sulfonylhydrazides as radical precursors. Mild radical generation from sulfonylhydrazide-based alkyl donors allows alkylation at 50 °C, obviating the need for alkyl halide precursors that require harsher conditions to activate, while enabling coupling with challenging secondary alkyl groups and heteroarenes that are poorly tolerated by existing methods. The reaction is scalable, exhibits broad functional-group tolerance across >70 examples and was applied to the synthesis of platisidines B and C.

S.-C. Kao,^† K.-J. Bian,^† J. C. Tang,^† S. Yu, Y. Wang, Y. Chen, X. Chen & J. G. West*

Nat. Catal. 2026 (DOI: 10.1038/s41929-026-01600-0) 🔓

The authors report an anti-Markovnikov hydroalkylation of unactivated alkenes using simple malonic acids as alkyl radical precursors. A traceless radical polarity reversal strategy uses a carboxyl group to temporarily alter radical polarity, enabling addition to otherwise polarity-mismatched electron-rich alkenes before in situ decarboxylation. The iron-and-thiol dual-catalytic platform enables hydromethylation, hydroethylation and hydrocyclobutylation, while fluorinated malonic acids provide access to mono- and difluoroalkyl motifs, with its utility demonstrated in the synthesis of a GPR119 agonist.

👉 C&EN write-up, here.

P. Visiedo-Jiménez, Q. Ordan, S.-J. Burlingham & F. Juliá-Hernández*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c13635) 🔓

The authors report an iron ligand-to-metal charge-transfer (LMCT) photocatalytic strategy for the direct decarboxylative borylation of non-activated aliphatic carboxylic acids, providing alkylboronic esters without prior substrate activation. The reaction exhibits broad functional-group tolerance, including complex drug-like and natural product-derived molecules, and provides scalable access to valuable organoboron building blocks from chemical feedstocks.

Z. Liang, Q. Yang, A. Ramkissoon, C. M. Shoen, M. Cynamon & S. B. Herzon*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c13738)

The authors report a divergent synthetic platform for accessing novel core-modified bicyclic pleuromutilins (BPs)—which lack the cyclopentanone ring, and C10/C11 substituents—and the natural tricyclic pleuromutilin skeleton from a common β-ketoester precursor. A multigram-scale bis(sulfonate) intermediate enables rapid C12 and C22 diversification through a single-flask, two-fold substitution, providing >30 BP analogues for antibacterial evaluation. Selected carbamate derivatives showed Gram-positive activity comparable to the pleuromutilin antibiotic tiamulin, with some also showing activity against Acinetobacter baumannii, cfr⁺ Staphylococcus aureus and mycobacteria. The route was further extended to new syntheses of (+)-mutilin and (+)-pleuromutilin.

S. M. Freeman,^† E. M. Landwehr,^† R. Tanaka,^‡ J. J. Rojas,^‡ J. B. Bailey, M. Gembicky & R. A. Shenvi*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c13989)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2025-490r9) 🔓

The authors report a decagram-scale synthesis of the Galbulimima (GB) alkaloid GB13 and its use as a common precursor to 11 GB alkaloids spanning three structural classes. A 9-step synthesis provides 12.97 g of GB13, enabling exhaustive study of its reactivity and late-stage scaffold remodelling, including complex rearrangements, twisted olefin intermediates and Pd- and Os-catalysed C–H functionalisation.

X. Wang,^† J. Luo,^† B. Wang, T. Long, J. Li, Y. Xu, S. Zou, Q. Zeng, Y. Yin, X. Xu, T. Han, H. Wang, Z. Liu, L. Tao* & C. Li*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c15393)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15003439/v1) 🔓

The authors report a scalable total synthesis of the polyether ionophores ecteinamycin and nonthmicin, featuring electrochemical decarboxylative alkenylation, an enzyme-catalysed anti-Baldwin cyclization and a redox-economic asymmetric C–C bond formation. The synthesis enabled systematic biological evaluation, revealing that nonthmicin selectively suppresses Clostridioides difficile, protects mammalian cells from toxin B-induced cytopathology, and exhibits therapeutic efficacy in a mouse model of C. difficile infection.

M. D. Glossbrenner, S. González-Granda, L. A. Farmer, E. A. Noten, S. Kamal, C. M. Balintfy, O. S. Nayal, D. A. Pratt & C. R. J. Stephenson*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10408)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2023-gw0xb/v2) 🔓

The authors report a photoredox strategy for the synthesis of vinyl sulfoximines from sulfinamides and vinyl bromides. The method redirects ambident sulfinamidyl radicals from thermodynamically favoured nitrogen reactivity towards kinetically favoured sulfur-centred C–S bond formation, enabled by rapid β-scission, providing broad access to vinyl sulfoximines with varied substitution. Enantioenriched sulfinamides undergo the transformation with high enantioretention, consistent with the configurational stability of the sulfinamidyl radical.

A. Khosravi & M.-Y. Ngai*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.3165931) 🔓

The authors review the development of cobalt-catalysed metal–hydride hydrogen atom transfer (Co–H/MHAT) as a platform for C–N bond formation from alkenes, from early nitrosation chemistry to recent asymmetric and photoredox approaches. Across reductive and oxidative Co–MHAT manifolds, a common Co–H-initiated radical/organocobalt intermediate can be channelled through radical–radical coupling, radical–polar crossover or radical ligand transfer, enabling hydroamination, hydroazidation, hydroamidation and remote amination. These complementary reactivity modes enable C–N bond formation at sterically hindered and electronically unbiased sites.

Q. Li,^† X. Gao,^† M. Zhang,^† J. Luo,^† B. Tan, M. Yang, Y. Xiang, M. Liu, S. Wang, Z. Zhou, W. Yi* & Z. Zeng*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.4582039)

The authors report the meta-selective nucleophilic functionalisation of pyridines via a dearomatisation–rearomatisation sequence. Single-electron oxidation of redox-active oxazino-pyridines enables nucleophilic capture and subsequent rearomatisation to furnish meta-functionalised pyridines. The method enables meta-alkoxylation using alcohols, as well as hydroxylation and halogenation, with broad functional-group tolerance and applicability to late-stage functionalisation of pharmaceuticals.

I. M. McWhinnie & D. W. C. MacMillan*

Chem 2026, Online Now (DOI: 10.1016/j.chempr.2026.103249) 🔓

The authors report a metallaphotoredox deoxygenative hydroalkylation of alkynes using alcohols as alkyl radical precursors, providing substituted olefins under mild conditions. The method exhibits broad alcohol and alkyne scope with excellent functional group tolerance, including the use of rarely exploited α-tertiary alkynes to access hindered 1,1-disubstituted olefins. The resulting olefins can undergo a second Markovnikov-selective hydroalkylation to generate quaternary carbon centres.

🧬 Medicine or Misuse? Anthropic has recently reported five cases in which scientists used its Claude AI for research involving viruses, venoms or toxins that could potentially be used in biological weapons development. The company does not assert that the researchers intended harm, but flagged the cases because some users attempted to circumvent its safeguards or obscure what they were studying.

The work being investigated sits firmly in dual-use biology: research that can have legitimate scientific or medical applications but could also be used to cause harm. One project investigated mutations in chikungunya virus that affect how efficiently it spreads and evades the immune system; another studied how avian flu viruses adapt to mammals and cause disease. Both are legitimate areas of infectious-disease research but could potentially be misused, creating the difficult challenge of distinguishing legitimate research from nefarious activity.

Some biosecurity experts see Anthropic’s cases as evidence of emerging AI-enabled biological misuse, while others argue that much of the research described is routine work needed to understand pathogens. However, bioweapons were only part of the story: Anthropic also identified Claude being used for cyberattacks, surveillance, fraud and weapons development.

The report arrives amid growing warnings from AI leaders about the pace of development. Anthropic CEO Dario Amodei has argued that frontier AI development needs to slow enough for safety measures to catch up, citing risks including bioterrorism alongside cyberattacks and loss of control over increasingly capable AI systems. A leading safety researcher at Anthropic, among others, has also warned that rapid AI advancement carries a >10% risk of human extinction within the next decade; however, many tech leaders also believe AI could cure all major diseases within the same timeframe…