Input (Alkene): Output (Carbocycle)

[2+1] and [2+1+1] Cyclization: Diversifying Alkenes for Small Carbocycles via Photocatalytically Accessed 1,3-Dielectrophiles

J. Jang,^† C. Kim,^† J. Won & S. Y. Hong*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.5c21279)

The authors report a strategy to access both cyclopropanes and cyclobutanes from alkenes, enabled by a single-component iodomethylthianthrenium reagent. The key to these transformations lies in harnessing the dual reactivity of photocatalytically generated 3-iodoalkyl thianthrenium to effect size-tunable ring formation. In the presence of a suitable base, a [2+1] cyclization is triggered via intermediacy of a thianthrenium ylide. The resulting cyclopropanated linchpin can be readily diversified through diastereoselective C(sp³)–N cross-couplings and a range of radical-mediated functionalizations. In contrast, treatment of the identical 1,3-dielectrophiles with methylene compounds and a milder base switches the reaction mode to a net [2+1+1] cyclization, selectively furnishing cyclobutanes in a modular fashion.

Copper-Catalysed Enantioconvergent Radical C(sp³)–C(sp³) Cross-Coupling of Tertiary Electrophiles with Cyclopropanols for Quaternary Carbon Formation

D. Gao,^† L.-Z. Qin,^† Z.-L. Li, Q.-S. Gu & X.-Y. Liu*

Nat. Synth. 2026 (DOI: 10.1038/s44160-025-00987-1)

The authors report a copper-catalysed enantioconvergent C(sp³)–C(sp³) cross-coupling of racemic tertiary electrophiles with easily accessed and bench-stable cyclopropanols under mild reaction conditions. Key to success is the rational design of quinine-derived N,N,N-ligands to form coordinatively saturated copper intermediates with low steric congestion around the metal centre to accommodate tertiary alkyl radicals.

Synthesis and Properties of Allylic, Benzylic, Propargylic and Allenylic Oxonium Ions

H. S. S. Chan, Y. Li, J. L. Sutro, D. S. Brown, R. S. Paton* & J. W. Burton*

Nat. Synth. 2026 (DOI: 10.1038/s44160-025-00964-8)

Despite extensive studies of trialkyloxonium ions, allylic, benzylic, propargylic, and allenylic oxonium ions remain poorly explored. Previous reports of well-characterized allylic and benzylic oxonium ions rely almost exclusively on constrained tricyclic oxatriquinane or oxatriquinacene scaffolds, with few examples on unconstrained systems. This work reports a general, modular strategy for the synthesis of allylic, benzylic, and hitherto unknown propargylic and allenylic oxonium ions on unconstrained scaffolds. Systematic permutation of substitution patterns enables access to a range of doubly substituted oxonium ions. Most species are sufficiently stable to be characterized by NMR spectroscopy at room temperature, and several unexpected reactivity patterns are disclosed.

A C₁-Homologative Trifluoromethylation: Light-Driven Decarboxylative Trifluoroethylation of Carboxylic Acids

F. Belnome, A. Pulcinella, S. Bonciolini, M. Lepori, O. P. Datsenko, Z. He, M. Gasparetto, P. K. Mykhailiuk, B. de Bruin* & T. Noël*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.5c21423)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2025-9jfwq) 🔓

The authors report a general approach for the decarboxylative trifluoroethylation of aliphatic carboxylic acids under near visible-light irradiation. The transformation proceeds via photoinduced generation of a carbon-centered radical that adds to a bench-stable sulfonyl hydrazone reagent derived from trifluoroacetaldehyde, followed by light-driven fragmentation to furnish the desired trifluoroethylated products. The reaction operates under mild conditions, exhibits broad substrate scope, including primary, secondary, and tertiary acids, and tolerates diverse functional groups.

Ring Constraint Strategy Enabled Cycloaddition of Oxazolones and Alkenes via Photoinduced Energy Transfer

W. Wang, Y.-C. Chang & M. K. Brown*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.5c20071)

The authors introduce a visible-light-mediated intermolecular [2+2] photocycloaddition for producing polysubstituted 2-aminocyclobutanols. By leveraging triplet energy transfer, oxazolones undergo [2+2] cycloaddition with various alkenes, both activated and unactivated. This approach is notable for its simplicity, mild conditions, broad substrate scope, and high regio- and diastereoselectivity, enabling complex molecule synthesis from readily available materials. Additionally, a highly unusual cycloaddition with vinyl cyclopropanes was also demonstrated to construct [6,5]-fused scaffolds.

Seven-Membered Azacyclic Allenes: Synthesis, Trapping, and Stereochemical Transfer Studies

G. M. Scherer,^† B. A. Janda,^† L. Q. Van Auken & N. K. Garg*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.5c14361)

The authors report the chemistry of seven-membered azacyclic allenes as a means to access ring-fused azepanes that possess up to three newly formed stereocenters. Seven-membered azacyclic allenes were found to outperform their six-membered counterparts in enantiospecific cycloaddition studies, consistent with computational predictions of enantiomerization barriers.

Leveraging Divergent Ligand-to-Metal Charge-Transfer Excited State Pathways for Catalyst Control over Alkoxyl Radical Reactivity

Z. Tang,^† Y. Lin,^† A. Mehmood, A. E. Lojko, J. A. Shah, N. J. Schwartzapfel, B. G. Levine & J. M. Lipshultz*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.5c22609)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2025-b2p6p-v2) 🔓

Recent advances in ligand-to-metal charge-transfer (LMCT) excitation have enabled the generation of heteroatom-centered radicals via metal–ligand bond homolysis, yet alternative LMCT pathways remain largely unexplored. The authors report a general strategy for controlling reactivity from LMCT excited states of titanium alkoxides, enabling tandem β-scission/Giese addition reactions of both scission-amenable and scission-recalcitrant alcohols. Through the use of electronically tuned Ti catalysts, divergent pathways involving metal–ligand bond homolysis or excited-state β-scission are selectively accessed. Intramolecular competition studies demonstrate that catalyst-controlled scission can accelerate β-scission by up to 10³-fold relative to free alkoxyl radicals, underscoring the impact of accessing excited-state scission reactivity.

Total Synthesis of (±)- and (+)-Euphohyrisnoid A

Z.-H. Ye, Q.-Q. Ao, Y.-C. Peng, X. Liu,* X. Lin & C.-C. Li*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c00187)

The first total synthesis of (±)- and (+)-euphohyrisnoid A, a highly rearranged lathyrane Euphorbia diterpenoid with a [5–7–6–6] tetracyclic core, was accomplished. The synthesis was guided by a mild intramolecular Diels–Alder (IMDA) reaction, which efficiently constructed the pivotal bicyclo[2.2.2] ring system with high diastereoselectivity.

Heterobenzyl Chlorides as Linchpins for C–H Arylation via Sequential C–H Chlorination/Cross-Electrophile Coupling

J. T. Floreancig,^† M. A. Lopez,^† A. R. Dick, L. Cardinale, N. C. Goodwin, D. L. Poole & S. S. Stahl*

ACS Catal. 2025, ASAP (DOI: 10.1021/acscatal.5c08221) 🔓

The authors report the arylation of heterobenzylic C–H bonds by using heterobenzyl chlorides as linchpins that can undergo Ni-catalyzed cross-electrophile coupling with aryl iodides. The results show different reactivity for primary and secondary heterobenzyl chlorides and also show differences among secondary heterobenzyl chlorides at different positions on the heteroaromatic ring. The Ni-catalyzed conditions identified for each of these substrate classes ensure that the rate of heterobenzyl chloride activation complements the rate of aryl iodide activation.

Arylhydrazines: Convenient Homogeneous Reductants for Scalable Cross-Coupling

N. Kurig,^† D. A. Cagan,^† K. C. Harper, Y. Kawamata, D. G. Blackmond* & P. S. Baran*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.9252206) 🔓

The authors introduce arylhydrazines as inexpensive, convenient reductants for Ni-catalyzed sp²–sp³ coupling of aryl halides and secondary alkyl iodides. Mechanistic studies support hydrazine-mediated Ni^II reduction for a Ni^I/Ni^III cycle, delivering improved yields, reproducibility, and scalability over Zn-based methods.

A Brønsted Acid-Base Approach for the Monoselective C-F Substitution of (Trifluoromethyl)alkanes

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

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.10001954/v1) 🔓

The authors disclose a method for the net coupling of nucleophiles with a single C–F bond of unactivated (trifluoromethyl)alkanes. The process proceeds through a base-promoted dehydrofluorination/defluorinative nucleophilic addition cascade to form vinyl fluoride intermediates, which undergo rapid hydrofluorination to yield gem-difluorinated products, thereby transforming aliphatic CF₃ groups in commercial building blocks and medicinal compounds into diverse α,α-difluoro(thio)ether motifs.

A Modular Approach to meta-Fluorinated Pyridines

O. Rushchak, V. Sham, B. Dansberg, A. Kysil, T. Yegorova & P. K. Mykhailiuk*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.10001883/v1) 🔓

Since 1947, the Balz-Schiemann reaction remains the most popular method for the synthesis of meta-fluorinated pyridines. It involves dangerous pyridyl diazonium salts, and numerous explosions have been documented in the literature. The last incident was reported only recently, in 2020. Here, the authors have developed a safe alternative to meta-fluoropyridines using a shelf-stable reagent.

Radical Deoxygenation of Alcohols via Visible Light Irradiation of a Titanium Porphyrin Catalyst

B. M. Gross, S. Razavi, A. J. de Almenara & B. M. Stoltz*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.10001933/v1) 🔓

The authors present the unique ability of a titanium porphyrin complex to directly deoxygenate alcohols without pre-activation. The system generates the carbon-centered radical under mild reaction conditions, turning over the catalyst by photoexcitation with purple LEDs. To demonstrate its preliminary value, the radical intermediate can further be utilized for Giese addition and nickel-mediated cross-coupling.

Skeletal Editing of Furans into Pyridines

P. Kafle,^† S. Yasuda,^† D. Herndon, D. Nilson, R. Fox, N. G. Akhmedov & I. Sharma*

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

The authors report a scaffold-hopping strategy in which a cyano sulfenylcarbene selectively cleaves the furan core to generate dienone intermediates bearing a thioaryl leaving group. A subsequent reaction with a nitrogen source restores aromaticity and yields pyridines, a privileged and pharmaceutically indispensable heterocycle. This metal-free process exhibits broad functional-group tolerance, enables ¹⁵N incorporation, and provides a conceptually distinct approach to controlled heterocycle remodeling.

PCET-Enabled Decarboxylative Oxygenation Promoted by Photoexcited Nitroarenes

A. D. Duke, S. Banerjee, A. P. Thupili, D. R. Pradhan, M. J. Vetticatt* & M. Parasram*

Chem 2026, Online Now (DOI: 10.1016/j.chempr.2025.102872) 🔓

The authors report that tuning the aromatic substituents of photoexcited nitroarenes enables selective decarboxylative oxygenation of carboxylic acids via proton-coupled electron transfer (PCET). This transformation represents a new reactivity mode for photoexcited nitroarenes, which are typically known as selective hydrogen atom transfer (HAT) reagents for hydridic C–H bonds. Mechanistic studies support PCET pathways and demonstrate that these reagents can be tuned to preferentially activate O–H bonds over weaker C–H bonds, enabling single-electron activation of challenging heteroatom–H bonds.

Preventing Cancer

🚬 Preventing Cancer. A global analysis in Nature Medicine has found that 7.1 million of 18.7 million new cancer cases in 2022—nearly 40%—were attributable to 30 modifiable risk factors, and therefore potentially preventable. Tobacco smoking was the single largest contributor (15% of cases), followed by infections (10%) and alcohol consumption (3%). Lung, stomach, and cervical cancers accounted for nearly half of the preventable cases.

The burden varied by sex and region: 2.7 million cases (30%) in women and 4.3 million cases (45%) in men were linked to modifiable risks. HPV-related cervical cancer predominated in low- and middle-income regions, whereas smoking was the leading cause in high-income settings. The authors concluded that targeted prevention, particularly around tobacco control, vaccination, and alcohol reduction, offers the most effective route to reducing future cancer cases.