L. Kong,^† K. Zong,^† M. Hopfengärtner, B. J. Orzolek & R. Shenvi*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003884/v1) 🔓

The authors describe an iron-catalyzed [1+1+1] synthesis of cyclopropanols through iterative outer-sphere reactions between two carbenes and an ester. The reaction first generates silyl enol ethers with high stereo-, regio-, and chemoselectivity via a traceless, directed olefination strategy, which are subsequently engaged in cyclopropanation to deliver the target products. This modular sequence enables transformations that are otherwise inaccessible using conventional approaches.

Y. Xu, Z. Liu, L. Chen, Y. Wang, X.-A. Chen, J. Wang & Y. Xu*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02166-x)

The authors report an efficient, mild protocol for converting aliphatic ketones into ketyl-type radicals using a bifunctional silyl reagent. By leveraging a radical translocation strategy, the method avoids strongly reductive conditions and enables integration with Pd catalysis to achieve redox-neutral ketone–olefin couplings. A range of alkenylation and allylation products were obtained from readily available olefins, rather than organometallic reagents, with broad functional-group tolerance.

K. Cui, Y. Li, S.-F. He, G. Zhang, D. Li* & T. Shen*

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01088-3)

The authors report an electrophotocatalytic decarboxylative vicinal dichlorination of aliphatic carboxylic acids using 1,2-dichloroethane as both solvent and chlorine source. Mechanistic studies suggest formation of an alkene intermediate via photocatalytic dehydrogenative decarboxyolefination, followed by electrochemical vicinal chlorination. The protocol proceeds under mild conditions, tolerates diverse functionality, and enables late-stage vicinal dichlorination of bioactive molecules and natural products.

M. Sodoor,^† J. D. Hart,^† A. W. Q. Koh, S. Nigam, C. Y. Ho, G. C. Y. Ng, H.-Y. Li & P. S. Grant*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05798)

The authors report a versatile skeletal editing strategy that converts phenols into 2-cyclopentenones through para- and ortho-carbon deletion. The transformation combines oxidative dearomatization, photorearrangement, and tandem decarboxylation/alkene isomerization, while a modified protocol enables the ring contraction of guaiacols to afford 2-(methoxycarbonyl)-2-cyclopentenones. The method was applied to a broad range of phenols, including natural products, and led to the identification of a novel anticancer hit compound.

S. Maiti,^† D. Baek^† & S. S. Stahl*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06785) 🔓

The authors report a practical alkene epoxidation method using the commercially available iron porphyrin Fe(TPFPP)Cl (0.05 mol%) and aqueous NaOCl in acetonitrile under ambient conditions without additional ligands or additives. Developed as an alternative to stoichiometric peroxyacids such as m-CPBA, which show poor compatibility with aromatic heterocycles and present scale-up hazards, this method exhibits broad substrate scope and high yields. Its practicality is demonstrated by the 100 g scale epoxidation of tri-O-acetyl-ᴅ-glucal, which reaches completion within 15 min at room temperature.

S. Adak, V. Muñoz-Canales, S. S. Manna, K. Raghavachari,* S. Ortega-Gutiérrez,* Q. Lefebvre, C. Salome* & M. K. Brown*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05064)

The authors validate [2]-ladderane derivatives as simplified 1,2-disubstituted cubane analogs and bioisosteres of ortho-substituted benzene. This study demonstrates the gram-scale synthesis of versatile [2]-ladderane building blocks and their functionalization through medicinal chemistry-relevant transformations. Matched pair analysis of bioactive compounds revealed favorable physicochemical properties alongside maintained biochemical and cellular activity.

N. J. Coradi & J. S. Bandar*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c04370) 🔓

The authors report a strategy for benzyl radical generation via consecutive deprotonation and single-electron oxidation. An HMDS base generates a low concentration of a benzyl carbanion that undergoes oxidation and trapping with TEMPO. Guided by C–H acidity and carbanion oxidation trends, the protocol enables functionalization of alkylarenes with high oxidation potentials and tolerance of weak C–H bonds and oxidatively sensitive functional groups, including pharmaceuticals and N-heteroaryls. The study further demonstrates that modulation of base strength can switch site-selectivity between distinct benzylic positions via a Curtin–Hammett-regulated oxidation pathway.

Y.-D. Zhu,^† T. Deng,^† H.-J. Jiang, N.-Y. Lu & L.-Z. Gong*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c04538)

While asymmetric S-functionalization of sulfenamides has recently emerged as an effective strategy for accessing chiral sulfilimines, methods enabling the creation of S-chirality via C(sp³)–H sulfimidation between sulfenamides and hydrocarbons remain limited and synthetically challenging. Here, the authors describe a photoinduced copper-catalyzed C(sp³)–H sulfimidation that enables the straightforward synthesis of highly enantioenriched sulfilimines from simple hydrocarbon feedstocks.

👉 For recent complementary work by X.-Y. Liu and co-workers on the enantioselective synthesis of sulfur-stereogenic alkyl sulfilimines via C(sp³)–H-derived alkyl radicals under copper catalysis, see, here.

J. D. Hart,^† J. K. Lawrence,^† P. N. Franqui, D. R. Perrott, B. Yi, Y. Xi, C. J. Sumby, C. G. Newton* & J. H. George*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06760) 🔓

The marine sponge-derived halenaquinone meroterpenoids share a strained diketofuran motif with the fungal viridin/wortmannin and plant-derived hibiscone natural product families, despite arising in evolutionarily distant organisms. Guided by biosynthetic logic, a collective synthesis of the halenaquinone family was developed featuring rapid assembly of the tetracyclic core through an aryne–furan Diels–Alder reaction, followed by divergent late-stage oxidations to access xestoquinone, halenaquinone and related congeners. The route enabled the synthesis of seven natural products, three structural reassignments and preliminary evaluation of their cytotoxic activity.

N. L. Magann,^† G. L. Barnes,^† R. Schioldager,^† F. M. Hörmann, R. Muñoz, H. Han, D. V. Hoff & C. D. Vanderwal*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06599)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2025-djk90) 🔓

The authors report concise syntheses of the marine alkaloids discorhabdin B and aleutianamine using a biomimetic rearrangement strategy. The route furnishes discorhabdin B in nine steps and aleutianamine in ten steps from a common pyrroloiminoquinone intermediate and was subsequently optimized to provide hundreds of milligrams of discorhabdin B. Biological evaluation revealed potent anticancer activity and showed that the more readily accessible discorhabdin B is equipotent to aleutianamine against pancreatic cancer cell lines.

W. Shen,^† S. Höthker,^† C. E. Hayter, N. K. Bowers, A. Pellegrini, S. Grimme* & M. J. Krische*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.9580914) 🔓

The first enantioselective alkynylations of aqueous fluoral are described using an iodide-bound ruthenium-(Ph-BPE) catalyst. The octahedral catalyst can exist as 12 diastereomeric-at-metal isomers, although calculations reveal that 2 isomers account for 99.9% of the Boltzmann population. In a Curtin–Hammett-type scenario, carbonyl addition proceeds predominantly through the less stable isomer.

L. Winfrey, G. S. Nichol, S. P. Thomas, D. R. Willcox* & M. J. Ingleson*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.9548215) 🔓

Three-component thio- and carbo-borylative cyclisations of ortho-alkynyl phenols using Et₂O·BF₃ and simple nucleophiles give functionalised benzoxaborinines and benzazaborinines. The nucleophile scope includes thioethers, thiols, and (hetero)arenes. Mechanistic studies distinguish direct thioether participation from thiol reactions proceeding via in situ formation of tri-thioboranes ((RS)₃B).

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

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003832/v1) 🔓

The authors report the first 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 likely misassignment at C40. The work further demonstrates regiochemical control in a gold-catalysed spiroketalisation through appropriate protecting-group selection and highlights the utility of a Buchner–Curtius–Schlotterbeck homologation for coupling highly functionalised fragments.

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

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003833/v1) 🔓

The authors complete the total synthesis of benthol A and confirm that the stereochemical assignment at C40 in the originally proposed structure was incorrect, despite having been supported by a highly confident computational analysis. Their multi-convergent strategy enabled access to this structurally intricate marine natural product in a longest linear sequence of 32 steps. The modular synthetic strategy should facilitate future studies aimed at identifying the structural features responsible for the compound’s antiplasmodial activity.

J. Luo,^† M. Wang,^† Q. Li, M. Liu, M. Yang, Y. Xiang, S. Wang, Z. Zhou, H. Gao, W. Yi,* Z. Zeng*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003991/v1) 🔓

The authors report a mild protocol for the meta-C–H acylation of pyridines via redox-neutral temporary dearomatization. The sequence combines cycloadditive dearomatization, synergistic N-heterocyclic carbene/photoredox-catalyzed acylation, and acid-promoted rearomatization, providing access to meta-acylated pyridines under mild conditions.

Z. Cui & H. Lu*

Chem. Soc. Rev. 2026, Tutorial Review (DOI: 10.1039/D5CS01298H)

This review presents a unified, bond-centric analysis of deaminative functionalisation strategies, reframing amines as versatile precursors for molecular editing rather than static end points. It organises recent advances by the types of C–C and C–heteroatom bonds formed through C–N bond activation, highlighting their utility in late-stage functionalisation and molecular diversification.

🐦 Not Just Winging It. From migratory birds and sea turtles to sharks and whales, many species are able to navigate vast distances using Earth’s magnetic field—an impressive feat considering that at any given moment an estimated 8–15 million of us are relying on Google Maps just to get from A to B. Yet despite decades of study, exactly how this biological compass works has remained a mystery.

Now, a new study published in Science has identified iron-rich immune cells in the liver of homing pigeons that appear to be essential for magnetic navigation when visual cues (i.e. the Sun’s position or familiar landmarks) are unavailable. The cells, known as macrophages, normally recycle old red blood cells and store iron inside a protein called ferritin. Surprisingly, these cells were found clustered near nerve fibres in the pigeons’ livers and exhibited superparamagnetic properties, meaning they can respond to magnetic fields.

To test whether these cells were involved in navigation, the researchers temporarily depleted macrophages in trained homing pigeons. Under sunny conditions, the birds navigated home normally using the Sun as a guide. But when released under completely overcast skies (when pigeons typically rely on magnetic cues) the macrophage-depleted birds became disoriented and failed to find their way home. None returned until the clouds cleared, suggesting that these liver-resident immune cells may act as biological magnetic sensors, transmitting directional information to the brain through nearby nerves.