K. Zhiliaev, T. Schreyer, M. V. Popescu & J. Mateos*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15008541/v1) 🔓

The authors report the direct synthesis of selenonium salts from bench-stable Se(III) cationic selenuranes via a simple dump-and-stir protocol under air at ambient temperature, without exogenous activators. The method enables selenonium formation across diverse arenes and complex molecules, with broad functional-group tolerance and predictable site selectivity. The resulting selenonium salts serve as versatile linchpins for photochemical, nucleophilic and transition-metal-catalysed transformations, enabling late-stage molecular diversification.

X. Zhang,^† R. Wu,^† Z. Liu,* G. Yin, J. Tang, P. Sivaguru, X. Hong,* E. A. Anderson & X. Bi*

Science 2026, First Release (DOI: 10.1126/science.aeh6251)

The authors report a general platform for the stereoselective assembly of chiral and meso tetrasubstituted bicyclo[1.1.0]butanes (BCBs) from alkynes and carbenes. Chiral BCBs are accessed through a stepwise [2+1+1′] cycloaddition of alkynes with two distinct carbenes, using triftosylhydrazones as carbene precursors and a sterically hindered chiral dirhodium catalyst to enable kinetic resolution of the cyclopropene intermediate with high enantioselectivity. A complementary one-pot [2+1+1] cycloaddition provides meso BCBs directly from alkynes, with both approaches exhibiting broad substrate scope and functional-group compatibility.

Y.-K. Qiu,^† Y.-P. Tang,^† C.-G. Zhang,^† Q. Huang, J. Li, L. Chen, Z. Wang & L. Dai*

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01147-9)

The authors report an enantioselective synthesis of 2-azaspiro[3.3]heptanes via chiral phosphoric acid-catalysed reductive amination. The method provides a broad range of enantioenriched 2-azaspiro[3.3]heptanes in high yields and excellent enantioselectivities, including derivatives of bioactive molecules. The resulting chiral building blocks were applied to the concise synthesis of several pharmaceuticals and an IRE1α inhibitor bioisostere with improved potency and ADME properties.

A. A. Kadam,^† K. Lee,^† Y. Liao, A. Knyazev, M. J. Lourenço, P. Tung, A. N. Cauley, J. M. Dones, M. S. Oderinde, J. Kempson & J. B. Roque*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c09936) 🔓

The authors report a nickel-catalysed migratory arylation of aliphatic amines using Katritzky salts, enabled by a “store-and-release” strategy in which dihydropyridines act as latent reservoirs to store translocated alkyl radicals before releasing them for arylation. The protocol enables regiodivergent deaminative arylation of Katritzky salts derived from diverse primary amines with a broad range of (hetero)aryl bromides, exhibiting broad functional-group tolerance, compatibility with pharmaceutically relevant substrates, and was further applied to small-molecule library synthesis.

D. A. Ray,^† A. B. Shaff,^† D. C. Obenschain & G. Lalic*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10362)

The authors report a copper-catalysed cross-nucleophile coupling of alkenylboronic esters and alkylboranes to access 1,2- and 1,1-disubstituted alkenes. Cross-selectivity is achieved by exploiting the ambiphilicity of organoboranes, with selective transmetalation of the alkenylboronic ester followed by formation of a boronate complex with the alkylborane.

R. Nsouli,^† H. N. Tran,^† R. S. Sidhu, H. G. Ford, A. V. Tran, H. Kaur, G. Galiyan & L. K. G. Ackerman-Biegasiewicz*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c07607) 🔓

The authors report a tunable 24-well photoreactor that enables independent control of wavelength, light intensity and irradiation time on a per-well basis for high-throughput screening of light-driven reactions. Benchmarking across Fe-catalysed, Ce-catalysed and Cu-mediated visible-light-induced homolysis transformations demonstrated excellent reproducibility across wells and comparable yields to conventional light sources. Application of the platform to Fe-catalysed decarboxylative Giese addition revealed pronounced ligand- and wavelength-dependent reactivity.

D. H. Lee,^† H. Kang,^† M. Ko,^† J. You, D. Kim, G. Bang, J. Y. Kim, H. J. Kwon* & Y. Park*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14447)

The authors report a mild photocatalytic oxygen-to-nitrogen skeletal editing strategy that converts furan-containing natural products into their pyrrole counterparts with high chemoselectivity. The method enables direct O-to-N editing of diverse bioactive natural products, including limonin. This single-atom edit redirects the primary biological target from the canonical kinase pathway to mitochondrial nicotinamide nucleotide transhydrogenase, transforming a cytotoxic natural product into a potent antifibrotic agent without measurable cytotoxicity up to 80 μM.

L. P. Pop & R. A. Shenvi*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10183)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15003543/v2) 🔓

The authors report a synthetic approach to the species-selective succinate dehydrogenase inhibitor siccanin that rapidly accesses its highly hindered cis-syn-cis drimane core and associated chemical space. The strategy addresses longstanding challenges in the synthesis of this scaffold, including stereocontrolled etherification and late-stage C15 oxidation. Computational studies were used to rationalize and predict conformational preferences, stereochemical outcomes and the reactivity of key O-centered radical intermediates, enabling the development of a concise route to siccanin.

R. Ye,^† P. He,^† L. Kan, T. R. Plambeck & G. Dong*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.2236309) 🔓

The authors report a redox-neutral palladium/norbornene-catalysed vicinal dialkylation of aryl boronic esters, enabling simultaneous installation of two alkyl groups at the ipso and ortho positions of arenes. The reaction tolerates a broad range of functional groups and accommodates diverse aryl boronic esters and α-carbonyl alkyl bromides. Mechanistic studies support an unusual radical-mediated pathway for the ipso alkylation and the method was applied to the streamlined four-step synthesis of a complex benzoazepane.

J. Brześkiewicz, K. Kapur, B. Maryasin & N. Maulide*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.3520541) 🔓

The authors report a deprotective alkylation strategy for the direct conversion of alcohols into secondary and tertiary amines using nonafluoromesitylenesulfonyl (Nms) amides. The method proceeds with high yields and stereospecificity across a broad range of alcohols and amine substrates, including complex drug-derived molecules. Its utility was demonstrated by a three-step (longest linear sequence) synthesis of Penfluridol and the efficient preparation of ¹⁵N- and deuterium-labelled amines.

E. N. George,^† M. C. Castillo,^† J. Z. Wang, C. Ahn & C. A. Gould*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15008631/v1) 🔓

The authors report a new electrochemical strategy termed “redox-metered paired electrolysis” that enables rate-matched generation of alkyl radicals from amine-derived dihydropyridines and activation of aryl electrophiles. Applied to deaminative C(sp³)–C(sp²) cross-coupling, the approach enables coupling across four classes of amine-derived radical precursors and five classes of aryl electrophiles, including aryl triflates and activated carboxylic acids. Nineteen amine/electrophile combinations are demonstrated across more than 75 examples, including seven previously unreported couplings.

Z. Zhang, S.-T. Kim, J. Li & G. Dong*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15008499/v1) 🔓

The authors report a late-stage carbonyl-to-¹⁵N skeletal modification that converts complex cyclic ketones directly into ¹⁵N-enriched saturated N-heterocycles. The method employs a methylsulfonyl-based ¹⁵N-azonation reagent that suppresses unproductive overoxidation, overcoming limitations of previous carbonyl-to-nitrogen swap chemistry. The reaction exhibits a broad substrate scope and tolerates a wide range of functional groups, enabling the labelling of diverse steroidal, natural product-derived and drug-like scaffolds.

S. Basuli,^† S. Maji,^† C. D. Clinton,^† S. Banerjee, D. R. Pradhan, L. Fioretto, J. S. Hirschi* & M. J. Vetticatt*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv-2025-mpgjm/v2) 🔓

The authors report that silver(II) fluoride (AgF₂) in acetonitrile acts as a mild source of fluorine radicals. Mechanistic investigation of the AgF₂-mediated fluorination of pyridine reveals that an acetonitrile-ligated AgF₂ dimer serves as a source of an electrophilic fluorine radical for H-atom abstraction. This insight was leveraged to develop a versatile fluorination platform using AgF₂ in acetonitrile as the sole reagent, enabling C(sp³)–H fluorination, decarboxylative fluorination, alkene difluorination and dearomative difluorination of heterocycles.

⚠ The Importance of Lab Safety. As synthetic organic chemists, we can become desensitised to working with hazardous chemicals but remaining cognisant about what we work with is vital to our own and our lab mates' safety. Two high-profile incidents at major universities occurring within 24 hours of one another and reported by Chemical & Engineering News are an important reminder of this.

At MIT, a chemistry building was closed for four days after a graduate student reported synthesising dimethylmercury, an exceptionally toxic organomercury compound (<0.1 mL can cause severe mercury poisoning). Thankfully, the student subsequently tested negative for mercury exposure, and the university later said emerging information had called into question whether dimethylmercury had actually been produced. Following decontamination and assessment, the building reopened on 31 August.

For many chemists, the incident will immediately bring to mind Karen Wetterhahn, a professor of chemistry at Dartmouth College who died from dimethylmercury poisoning in 1997 after a few drops of the compound landed on her latex glove. At the time, she was following the recommended safety procedures but subsequent testing found that dimethylmercury could permeate latex gloves in 15–30 seconds. Around five months after the exposure, she began experiencing severe neurological symptoms. Her blood mercury concentration eventually reached 4,000 μg/L and, despite aggressive chelation therapy, she died aged 48, ten months after the exposure.

There had been other fatal incidents involving dimethylmercury, including one in the early 1970s in which a chemist died after preparing 6 kg of the compound, but it wasn't until Prof. Wetterhahn's death that a major reassessment of dimethylmercury's handling took place, with safety recommendations revised and safer alternatives adopted. Her legacy lives on through the Karen E. Wetterhahn Graduate Fellowship in Chemistry, established in 1998.

In a separate, fatal incident, a graduate student at Hokkaido University died on 27 August following severe exposure to hydrofluoric acid (HF). Two students who attempted to assist sustained minor injuries. HF is particularly hazardous because it can penetrate the skin with a delayed onset of pain; the fluoride ion can then bind systemic calcium, causing severe hypocalcaemia, tissue destruction and potentially fatal cardiac arrhythmias. The City of Sapporo has since cited Hokkaido University for four violations of Japan’s poisonous substances control act, including deficiencies in HF record-keeping, storage-key management and hazardous-substance labelling.

While we don't know what led the first graduate student to believe they had synthesised dimethylmercury, it is an important reminder that reaction work-up, purification and choosing the appropriate waste stream all form part of the risk profile, as these steps can also generate hazardous materials. These considerations are no less important than more typical concerns such as reagent and solvent compatibility, understanding the reaction mechanism, and considering potential side- and by-products before any reaction begins.

One useful resource is Leslie Bretherick's “Handbook of Reactive Chemical Hazards”, a compilation of documented hazardous reactions, chemical incompatibilities and laboratory incidents. Bretherick began compiling it after noticing that similar laboratory accidents involving the same chemicals had been reported more than once. First published in 1975, the handbook has been repeatedly updated and expanded, growing into a comprehensive reference covering thousands of documented hazardous reactions and incidents.