Y. Qin, P. Ren, J. Hu, S. Pradhan, T. H. Vuong, X. He, L. Alluhaibi, N. Rockstroh, S. Monti, G. Barcaro, A. Jaworski, P. Kuśtrowski, J. Rabeah, D. Hohenberger, S. Bagnich, A. Köhler, J. Breu, G. Vilé, M. Beller* & S. Das*

Science 2026 (DOI: 10.1126/science.aed6068)

A heterogeneous iron photocatalyst enables the oxidative cleavage of alkenes using CO₂ as the sole oxygen source under ambient conditions, providing ketones and carboxylic acids without hazardous oxidants. The method is applicable to a broad range of activated, unactivated and complex alkenes, displaying excellent tolerance toward oxidation-sensitive functional groups. Isotopic labeling, spectroscopic studies and quantum mechanical simulations confirm oxygen transfer from CO₂ and provide insight into the photocatalytic reaction pathway.

Y. Wang,^† J. Sun,^† Y. Li,^† D. A. Cagan,^† O. T. Ring, X. Zeng, J. Tsien, L. Massaro, J. E. Smith, B. J. Orzolek, M. R. Collins, Y. Kawamata & P. S. Baran*

Science 2026, 392, 1075–1081 (DOI: 10.1126/science.aef6981)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.10001512/v2) 🔓

The authors report a scalable, nickel-catalyzed stereoretentive radical-radical cross-coupling between enantioenriched sulfonylhydrazides and primary or secondary alkyl halides. The redox-neutral, substrate-controlled process proceeds without chiral ligands, directing groups or external redox reagents and delivers diverse piperidine and pyrrolidine derivatives in up to 90% yield and 80–96% enantiospecificity. Mechanistic studies support caged radical rebound at nickel, followed by Ni(I)/Ni(III)-mediated radical capture and reductive elimination.

N. Yalamanchili, J. H. Alexandre, R. L. Anderson & G. Zuccarello*

Nature 2026 (DOI: 10.1038/s41586-026-10692-4)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2026-qwhqp/v3) 🔓

The authors report an approach for generating chiral hydrogen atom transfer (HAT) catalysts in situ through the non-covalent self-assembly of chiral phosphoric acids and commercially available 2-mercaptopyridines. In this system, the phosphoric acid acts as a modular chiral element that imparts chirality to an otherwise achiral thiol, enabling access to a broad combinatorial space of chiral HAT catalysts. The resulting platform enables the photochemical deracemization of 2-aryl pyrrolidines via an enantioselective hydrogen atom relay, in which a single chiral assembly mediates both hydrogen atom abstraction and delivery.

J.-J. Yin, S.-G. Xin, H. Cao & L. Zhang*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02156-z)

The authors report a modular and diastereoselective synthesis of sterically congested cyclobutane amino nitriles (CBANs) from commercially available ketones or aldehydes. The strategy exploits the unique reactivity of triplet nitrenes to enable a diradical-mediated ring expansion of alkylidenecyclopropanes, followed by titanium(IV)-catalysed cyanylation. Supported by experimental and computational studies, the method provides access to diverse vicinally substituted and spiro-fused CBANs with broad functional-group tolerance, including medicinally relevant motifs.

S. Xu, H. Judd, X. Z. Sui, P. Liu* & A. H. Hoveyda*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02164-z)

The authors present a divergent alkaloid remodelling strategy centred on isolable platforms generated by Hofmann elimination. Site-selective piperidine deconstruction through C–N bond cleavage and alkene formation enabled subsequent Stevens and Meisenheimer rearrangements, followed by ring-closing metathesis or intramolecular hydroamination to generate expanded and contracted frameworks. Using a limited set of catalysts and reagents, 26 distinct frameworks were synthesised in 48 total steps. The approach also revealed a reverse-Meisenheimer rearrangement and a rare anionic [1,6]-sigmatropic rearrangement. Biological evaluation across ten cancer cell lines identified expanded and deconstructed frameworks with micromolar and nanomolar activities, respectively.

L. Dai,^† G. Yin,^† Z. Tuo,^† Z. Chang,^† X. Xia, Z. Zuo, Y. Hu, S. Li, S. Kuang, Y. Lai, T. Wang, C. Wang, C. Qin, X. Li & W. Zhou*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02167-w)

The authors report a nickel-catalysed endo-stereoselective [2+2] cycloaddition of norbornadienes (NBDs) with unactivated internal alkynes, enabled by ligand-mediated facial differentiation of NBDs and nickel-controlled configuration of a key intermediate. The method provides efficient access to valuable scaffolds, including endo-tricyclononadienes and substituted homocubanes, with excellent atom economy. The scalability and utility of the reaction are demonstrated through applications in asymmetric catalysis and the synthesis of drug analogues.

C.-Y. Chen, Z. Fan, D. A. Strassfeld, H. S. S. Chan, M. C. Suarez, M. E. Hoque & J.-Q. Yu*

Nat. Catal. 2026 (DOI: 10.1038/s41929-026-01548-1) 🔓

The authors report a Pd-catalyzed site- and diastereoselective C3 C(sp³)–H arylation of saturated azacycles enabled by oxidation of the endocyclic amine to an N-oxide directing group. This one-bond extension strategy promotes favorable five-membered cyclopalladation and exploits the axial conformational preference of the N-oxide to selectively activate syn-axial C3 C–H bonds. The method provides broad access to functionalized piperidines and related saturated azacycles with predictable regio- and diastereoselectivity.

L. J. Harstad & D. W. C. MacMillan*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c03814) 🔓

The authors report a three-component anti-Markovnikov oxyalkylation of unactivated alkenes enabled by a metallaphotoredox-mediated "triple radical sorting" mechanism. The protocol couples alkenes, benzoic acids, and redox-active esters in a single step, exhibits broad substrate scope including complex drug-like molecules and is readily scalable. Furthermore, a one-pot oxyalkylation/deprotection sequence provides direct access to free alcohols without intermediate purification.

H. Hatano, V. A. Fernandes, S. Mukherjee, C. Zhu, A. Takahira, P. Jiang, M. Jin, Y. Harabuchi, R. Staub, M. Gao, A. Varnek, S. Maeda, N. Tsuji* & B. List*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06916) 🔓

The authors report a highly enantioselective Markovnikov hydration of electronically neutral alkenes with water. By combining confined imidodiphosphorimidate (IDPi) Brønsted acid catalysts with perfluorinated solvent–organized hydrogen-bonding networks, catalytic alkene protonation becomes viable under cryogenic conditions. The method affords tertiary alcohols in high yields and enantioselectivities, and further enables the formal deracemization of racemic tertiary alcohols through a temperature-controlled dehydration–rehydration sequence.

D. A. Brunner, D. C. Thomas, K. R. Steenback, S. D. Rozema & A. McNally*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c08076) 🔓

The authors report a strategy to overcome the poor regio- and site-selectivity of Minisci reactions in pyridines using C4-phosphonium salts as activating groups. These promote selective radical addition to phosphonium-bearing pyridines over unmodified heterocycles in polypyridine systems, while simultaneously acting as blocking groups to direct alkylation to the 2-position. Under photoredox conditions, alkyl bromides undergo acid-free Minisci coupling, and the resulting C–P bond can be readily cleaved during workup or leveraged as a versatile handle for the synthesis of 2,4-disubstituted pyridines. Control over the site of phosphonium installation further enables site-selective switching in complex drug-like structures.

X.-X. Wang & L. Jiao*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c02010)

The authors report a Pd-olefin-catalyzed ortho-alkylation of bromoarenes that retains the valuable C–Br bond. The reaction employs a synergistic ligand system comprising a newly designed imidazole-olefin ligand and a bulky phosphine, enabling the functionalization of a broad range of bromoarenes. Mechanistic studies reveal that the imidazole ligand suppresses unproductive C–C reductive elimination while promoting alkylation through secondary coordination to the palladacycle intermediate. The resulting insights enabled reduced ligand loadings and provided a practical route to complex polysubstituted arenes.

J. E. Budwitz,^† S. A. Hollers,^† A. R. Wester & C. G. Newton*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06794) 🔓

The authors introduce 2-triazenyl furans as bench-stable, electron-rich dienes for Diels–Alder reactions, providing convergent and divergent access to highly substituted arenes under redox-neutral conditions. The triazene group both activates the furan toward cycloaddition and promotes in situ aromatization, while also serving as a versatile handle for subsequent functionalization. The platform is compatible with a broad range of dienophiles and enables concise annulative syntheses of pomalidomide, (S)-apremilast, and related analogues.

F.-Q. Ni,^† Z. Wang,^† Z. Li, B.-F. Zhang, P. Zhang* & H.-H. Lu*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.5c21637)

The authors report a short enantioselective total synthesis of (+)-shearilicine enabled by machine learning-guided ligand design for a Pd-catalyzed α-arylation. A support vector regression model was used to virtually screen >120 BI-DIME-type ligands, identifying candidates that substantially improved the enantioselectivity of a challenging α-arylation between a highly functionalized cyclohexanone and a carbazole.

D. Nagornîi, Á. Valdés-Maqueda, S. Stocchetti, N. Kaplaneris, Z. He, J. H. A. Schuurmans & T. Noël*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c04790)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15000577/v2) 🔓

The authors report a flow-enabled platform for the late-stage installation of NCF₃ and SCF₃ groups onto arenes through coupling of flow-generated heteroatom–CF₃ anions with aryl thianthrenium salts. On-demand generation of NCF₃ and SCF₃ anions is combined with a copper-mediated photocatalytic cross-coupling, enabling the formation of aryl–NCF₃ and aryl–SCF₃ bonds under mild conditions. The method exhibits broad substrate scope and functional group tolerance, and is applicable to the late-stage diversification of medicinally and agrochemically relevant molecules.

A. S. Pollatos, Y. Kawamata & P. S. Baran*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15004225/v1) 🔓

This Account argues that electrochemistry has evolved from a niche, problem-solving tactic into a strategic platform for total synthesis, driven by the availability of standardized electrochemical equipment and the development of enabling methodologies, particularly electrochemical radical cross-couplings. Using historical examples alongside case studies primarily from the Baran laboratory, as well as selected contributions from other groups, the authors illustrate how electrochemical methods enable selective functionalization, site-selective C–H functionalization, decarboxylative functional-group interconversions, and convergent formation of C–N, C–O, C(sp²)–C(sp³), and C(sp³)–C(sp³) bonds. Particular emphasis is placed on electrochemically enabled radical retrosynthetic disconnections that simplify route design, reduce protecting-group usage and unnecessary redox manipulation, and allow coupling of densely functionalized fragments that are otherwise difficult to unite using conventional two-electron chemistry.

M. Puriņš, C. Elgindy & M. D. Levin*

Chem. Rev. 2026, ASAP (DOI: 10.1021/acs.chemrev.5c01009)

Recent advances have enabled shape-conserving replacement of individual atoms within molecular skeletons, establishing skeletal editing as a promising strategy for molecular optimization. This review presents a framework for categorizing atom-replacement reactions and discusses key concepts including skeletal rotation, vestigial substituents and retrosynthetic simplicity. Representative examples are surveyed, with emphasis on aromatic C-to-N replacement before expanding to other aromatic and aliphatic atom-replacement reactions. Remaining challenges and opportunities are highlighted, particularly in underdeveloped areas of aromatic and aliphatic atom replacement.

🌈 🔭 Celestial Rainbow. Nature has released its selection of the best science images of May, including winners from the 2026 Milky Way Photographer of the Year competition. Now in its ninth year, the competition showcases 25 extraordinary images, from remote deserts and mountain peaks to rugged coastlines and isolated islands.

One standout image, ‘My Perfect Night’ by Daniel Viñé Garcia, was taken deep within the Argentine Puna region of Catamarca. Reachable only by 4×4 vehicles and sitting at nearly 4,000 metres above sea level, the remote salt flat located near the small village of Antofalla (home to just 60 residents) offers exceptionally dark skies as electricity is generated locally and switched off at night. Garcia's image captures the southern hemisphere's Milky Way stretching across the sky, with the galactic centre and the Gum Nebula creating a natural balance across the scene.

The collection also features a remarkable diversity of landscapes and celestial events. Highlights include a panorama of the Geminid meteor shower on La Palma, the Milky Way rising over the geothermal waters of Yellowstone's largest hot spring, and Perseid meteors streaking across the sky above Dorset's iconic Durdle Door.