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N. J. Flodén, A. Collauto, P. H. Seeberger & R. Kumar*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c07870) 🔓

The authors report a light-mediated strategy to access hydrogen radicals (H•), the smallest radical in the universe, under synthetically useful conditions. A hydrazine–thiophenol system enables mild, metal-free hydrogenation of highly functionalized alkenes and hydrodehalogenation of alkyl and aryl halides, while tolerating diverse functional groups and stereochemical complexity. EPR, spectroscopic and computational studies support H• generation through fragmentation of a Rydberg radical intermediate.

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

Science 2026, 393, 910–916 (DOI: 10.1126/science.aej0194)

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

The authors report 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, before engaging a second carbene to form the cyclopropanol products with high cis-selectivity.

Z.-X. Zhang,^† K. Shu,^† M. V. Popescu,^† Y. Guo, J. L. Tyler, R. S. Paton* & V. K. Aggarwal*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02238-y)

The authors report a programmable, light-driven intramolecular [2+2] photocycloaddition of aza-1,5-dienes that overrides the classical ‘rule-of-five’ preference for 5-exo-trig closure. Tuning the electronics of an easily removable amide N-substituent switches the cyclization pathway between 5-exo-trig and the rarely observed 6-endo-trig mode, providing selective access to bridged [2.1.1] and fused [2.2.0] heterobicycles, respectively. Computational studies reveal how electronic and steric effects control the observed regiodivergence.

Y. Kuang,^† D. Zhou^† & M. Tomanik*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c12509) 🔓

The authors report a palladium-catalysed strategy for remote C–C bond formation enabled by through-space alkyl-to-alkyl palladium migration. An initially formed σ-alkylpalladium intermediate undergoes translocation through distal C(sp³)–H activation, enabling C–C bond formation at a site remote from the initial catalyst installation. The two-component annulation of 2-bromoanilines or 2-bromophenols with allylic bromides provides complex tricyclic heterocycles from simple precursors, with broad substrate scope and excellent heteroatom compatibility. Mechanistic studies support a migration pathway driven by relief of steric congestion at the palladium centre.

S. R. N. Kolusu,^† M. Rodríguez-Martínez,^† C. Aira-Rodríguez,^† M. Caldari, G. Brenlla-Carballo, I. Amado-Amado, E. Azzi, Y. Song, J. Ward, N. Selmi, J. A. Varela & M. Nappi*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c12120) 🔓

The authors report a metal-free strategy for reductive couplings of aliphatic carbonyls with unsaturated systems via nucleophilic photoactivation. A phenothiazine catalyst forms a hemiaminal intermediate with the carbonyl, which undergoes visible-light-induced fragmentation to generate alkyl ketyl radicals under mild conditions. The method enables coupling with diverse alkenes and alkynes, including the synthesis of Z-allylic alcohols and on-DNA functionalisation.

T.-Y. Peng,^† E. Y. K. Tan,^† T. Wakabayashi, Y. Liu & S. Chiba*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14314)

The authors report a photocatalytic platform for the skeletal remodeling of diazines into diazoles via formal ring contraction. Pyrimidines and pyridazines are converted to imidazoles and pyrazoles, respectively, through either rehybridizative transposition or deletion of an aromatic carbon unit. Photocatalytic single-electron transfer generates dearomatized diazacyclohexadienyl anions, which undergo disrotatory 6π-1,5-electrocyclization to drive the ring contraction.

H. Tao, Z. Huang & H. Lyu*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c13223) 🔓

The authors report a new class of chiral gem-diborylalkane reagents featuring two chemically distinguishable boryl groups, enabling selective and stepwise functionalisation. The reagents undergo diverse stereospecific transformations, including the construction of boron stereogenic centres, synthesis of boron-containing pharmaceuticals and preparation of drug intermediates.

M. Zhang, H. Yu, X. Huang & M. Dai*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c12593) 🔓

The authors report the first total synthesis of (±)-stemocurtisine, a rare insecticidal Stemona alkaloid featuring a cage-like polycyclic skeleton, characteristic pyrido[1,2-a]azepine ring system and highly oxidized tetrasubstituted double bond. Key to the synthesis is a palladium-catalysed cyclopropanol ring-opening carbonylative lactonization to construct a bicyclic lactone embedded within the target framework, and a hydrogen-borrowing strategy enabling concise, redox-neutral formation of the pyrido[1,2-a]azepine ring system through two intramolecular C–N bonds, delivering the natural product in 15 steps.

X.-Y. Wang, K. Lu, W. Jiang, L. Zheng, X.-M. Zhang,* F.-M. Zhang, H. Wang & Y.-Q. Tu*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c12963)

The authors report a 13-step asymmetric total synthesis of (−)-cribrostatin 4, enabled by an asymmetric double hydrogenation of 2,5-diketopiperazine-derived enamides using a novel spiropyrrolidine-derived diphosphine ligand. Mono- and oxidative Pictet–Spengler cyclizations provide expedient access to the tetrahydroisoquinoline and benzo[3.3.1]-bridged rings. Notably, hydrogen-borrowing catalysis enables late-stage stereochemical editing through the unprecedented direct β-epimerization of a primary alcohol.

S. Cheng, C. Ma, X. Chang,* J. Chang* & B. Yu*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.3399600)

This Review surveys molecular editing strategies for late-stage diversification of natural products and drug molecules, highlighting their potential to streamline analogue synthesis and lead optimization. The authors classify recent approaches into skeletal and peripheral editing, with representative examples illustrating their utility in the direct editing of complex molecules. Biomimetic molecular editing is also briefly discussed as a complementary strategy.

N. Hölter,^† F. Katzenburg,^† F. Boser & F. Glorius*

Angew. Chem. Novit 2026, 2, e70032 (DOI: 10.1002/anov.70032) 🔓

The authors provide a practical review of machine learning in synthetic organic chemistry, covering applications in reaction prediction, optimisation and synthetic method development. The review focuses on practical considerations, including data requirements, workflow integration and common pitfalls, and also discusses emerging applications of large language models and agentic workflows in the laboratory.

J. O. Imasuen, B. Jiang, M. Sofiadis, K. C. Harper, D. Yamamoto, T. Imai, A. S. Pollatos, P. Neigenfind, Y. Kawamata & P. S. Baran*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15007839/v1) 🔓

The authors report simultaneous two-directional radical cross-coupling of bifunctional radical precursors, enabling both ends of a molecular scaffold to be functionalized in a single operation. Diacid-derived bis-redox-active esters undergo Ag–Ni electrocatalytic decarboxylative arylation to access functionalized dibenzyl amines, while diamine-derived bis-sulfonyl hydrazides undergo redox-neutral deaminative radical cross-coupling to furnish diarylated carbon skeletons.

E. Cotter, L. Abounader & R. A. Shenvi*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15007797/v1) 🔓

The authors report a robust, non-aqueous variant of the Rh-catalyzed Hayashi–Miyaura conjugate addition that enables coupling of highly labile heterocyclic and heteroaryl boronic acids. Commercially available bisphosphine ligands and cesium salts minimize competing protodeborylation while enabling ligand-controlled anti-Fürst–Plattner additions. Experiments with a conformationally locked decalenone support the proposed role of torsional strain in controlling Fürst–Plattner selectivity and demonstrate that this intrinsic preference can be overridden, providing access to cis-3,5-disubstituted cyclohexanones and other medicinally relevant scaffolds.

K. K. Chung,^† C. A. Rivera,^† D. E. DeWeese,* N. K. Garg,* F. M. Ippoliti* & D. J. Nasrallah*

Nat. Rev. Chem. 2026 (DOI: 10.1038/s41570-026-00872-1)

The authors report a 2026 survey of 753 US adults examining perceptions of organic chemistry, finding that only 30% correctly identified it as the chemistry of carbon-based molecules; even among respondents who had taken organic chemistry, only 39% selected the correct definition. The survey also reveals limited recognition of organic chemistry’s contributions to medicines, materials and other areas of society, with many respondents failing to appreciate the broader benefits of the subject. The authors call on chemists and educators to improve public engagement with the field.

🎤 Dolly Parton: A Life Beyond Music. Known as the “Queen of Country”, Dolly Parton was one of the most successful musicians in history. Born into a poor farming family in Tennessee as one of 12 children, she went on to build a remarkable legacy beyond music, using her success and fortune to support vaccine research, healthcare and childhood literacy. Following her death at 80, Nature has highlighted the extent of her contributions to science and beyond.

In March 2020, Parton donated $1 million to Vanderbilt University Medical Center, establishing the Dolly Parton COVID-19 Research Fund. The money helped support early research into an experimental mRNA vaccine that would eventually become Moderna’s COVID-19 vaccine. The fund is acknowledged in the first published clinical study of the vaccine and has since been credited in at least 37 research papers. Parton later received her own vaccine publicly, encouraging others to do the same (see the video above) and even rewriting her song Jolene for the occasion: “Vaccine, vaccine, vaccine, vaccine, I’m begging of you please don’t hesitate.”

Her philanthropy extended far beyond vaccines, supporting paediatric and infectious-disease research, hospitals and HIV/AIDS fundraising. She was also the namesake of Dolly the sheep, the first mammal cloned from an adult cell, after a researcher suggested the name because the donor cells came from mammary tissue (Parton later said she was flattered by the tribute).

In 1995, she founded the Imagination Library—a programme that sends a free book each month to children from birth to age five—as a tribute to her father, who was unable to read or write. The programme now sends millions of free books to children every month, with one in six US children under five receiving them. Parton could easily have kept her considerable wealth for herself, but instead repeatedly put it to work helping others. She even helped transform her home state of Tennessee, opening Dollywood in 1986 and creating thousands of jobs while attracting tourists to the region around her hometown.

In an age when some of the world’s wealthiest people would rather spend billions on private spaceflight, Parton spent her fortune improving life here on Earth. Her legacy extends beyond the music she leaves behind to the millions of lives she helped improve.

Perhaps fittingly, some of the advice Parton gave to graduates of her Imagination Library is just as relevant to all of us: