Z. Huang,^† T. Wu,^† Z. Yuan, C. Meng, L. C. Garman, I. A. Guzei, B. Wu* & D. J. Weix*

Nature 2026 (DOI: 10.1038/s41586-026-10800-4)

The authors report a stereoretentive C(sp³)–C(sp³) cross-electrophile coupling strategy enabled by a “metallo-Curtius” process, in which readily available α-amino acid and α-hydroxy acid derivatives undergo stereoretentive decarbonylation analogous to the classical Curtius rearrangement. The resulting chiral alkylnickel intermediates subsequently undergo cross-coupling with alkyl radicals derived from alkyl iodides, providing access to stereocontrolled C(sp³)–C(sp³) bond formation from abundant chiral building blocks.

Y. Guo,^† Y. Li,^† B. Buchberger, Y. Liu, C. Capone, T. Adak, S. Ojha, J. L. Tyler, P. Neigenfind, M. Nassir, Y. Kawamata,* V. K. Aggarwal* & P. S. Baran*

Nature 2026 (DOI: 10.1038/s41586-026-10807-x)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15001005/v1) 🔓

The authors report a practical approach to C-aryl glycosides using glycosyl sulfonyl hydrazides as redox-neutral radical precursors for cross-coupling. Prepared directly from unprotected native sugars, these reagents generate glycosyl radicals under mild conditions and enable efficient access to diverse C-aryl glycosides, including all approved SGLT2 inhibitors for type 2 diabetes, as well as natural products such as salmochelins and neopetrosins. Beyond anomeric functionalization, the platform enables C–C bond formation at multiple positions on carbohydrate scaffolds and supports stereoretentive radical coupling that can override inherent stereochemical biases.

T. Pal, M. S. Sk,^‡ Y. C. M.,^‡ S. Kar, A. Ghosh & D. Maiti*

Nature 2026 (DOI: 10.1038/s41586-026-10826-8)

The authors report an O-allyl amido ester (OAAE) ligand-enabled palladium-catalyzed activation of distal γ-methylene and methine C(sp³)–H bonds in unbiased aliphatic carboxylic acids. The method converts readily available fatty and cyclic acid feedstocks into desaturated γ-lactones and γ-spirolactones through sequential C–H activation, dehydrogenation and cyclization. The utility of the strategy was demonstrated through the three-step synthesis of muricatacin and related analogues from margaric acid.

Z. Jia, H. A. Salazar, J. Tsien, Y. Ma, O. L. Coyle, E. Crossley, R. Alvarado, Y. Kanda, N. Williams, S. Chen* & T. Qin*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02196-5)

The authors report a concise and scalable synthesis of bridgehead-substituted [2]-ladderanes from readily available precursors. These strained hydrocarbons serve as versatile intermediates for regioselective bridgehead functionalization and strain-release cycloadditions, providing access to an array of multisubstituted bicyclo[2.2.2]octanes (BCOs). The resulting BCO scaffolds can be further diversified and applied as saturated benzene isosteres in pharmaceutically relevant molecules, leading to enhanced three-dimensionality and tunable physicochemical properties.

Y. Luo, J. Zhou, M. D. Mandler, E. E. Kwan & R. Y. Liu*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c07104)

The authors report a Pd-catalyzed decarboxylative coupling of hydroxamic acids with aryl (pseudo)halides that enables carboxylic acid derivatives to serve as surrogates for primary amines. The transformation proceeds through a tandem Lossen rearrangement/C–N cross-coupling sequence and provides efficient access to secondary amines from a broad range of alkyl and aryl hydroxamic acids, and aryl electrophiles. Mechanistic studies support a dual role for palladium in promoting both the Lossen rearrangement and the C–N bond-forming step.

E. Sfreddo, A. Durdevic, A. Palone, T. von Münchow, N. Matera, A. Mazzanti & P. Melchiorre*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c09924) 🔓

The authors report a stereoretentive Norrish–Yang photocyclization of enantiopure aryl alkyl ketones enabled by hydrogen-bond-guided conformational control of photogenerated 1,4-diradicals. The strategy promotes cyclization while suppressing competing Norrish type II fragmentation and stereochemical erosion, providing access to highly enantioenriched spirocyclobutanol-containing amines and related cyclobutanols bearing two stereocenters.

B. B. Botlik, A. N. Vieira,^‡ B. Mitschke,^‡ F. Ruepp & B. Morandi*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c08509)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2025-b0fgk) 🔓

The authors report an iron(II)-catalyzed C=C/N=O metathesis and its application to the mild oxidative decarboxylation of carboxylic acids. The one-pot reaction proceeds under air using inexpensive reagents and an earth-abundant iron catalyst, exhibiting broad functional-group tolerance, scalability and applicability to the late-stage modification of drug molecules. A complementary C=C/O=N metathesis provides access to imines instead of ketones, while extension of the methodology enables the synthesis of esters from α-aryloxy and α-alkoxy carboxylic acids.

L. Tao,^† Y. Niu,^† Y. Chen,^† Z. Yan, K. Wang, L. L. Liu, P. Yu* & Z. Dong*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c03854)

The authors report a ZnBr₂-enabled, enantiospecific “Homo-Boron-Wittig” cyclopropanation that converts chiral epoxides into cyclopropylboronic esters using boron-stabilized α-carbanions derived from geminal diboryl alkanes. The method accommodates a broad range of epoxide substitution patterns and provides densely substituted cyclopropanes, including tertiary boronic esters and tri-, tetra- and pentasubstituted cyclopropanes, with excellent enantiospecificity. Subsequent diastereoconvergent radical cross-coupling improves diastereoselectivity while preserving enantiopurity.

W. Zhang, Z. Lei, T. Liu, X. Guo, J. Shen, J. Su, Y. Li, J. Wu, H. Jiang, H. T. Ang, Y. Luo,* X. Guo, Y. Lan* & J. Wu*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c03412)

The authors report a ligand-regulated metallaphotoredox-catalyzed aminoarylation of ethylene that provides direct access to N-(hetero)aryl-substituted arylethylamines from readily available arenes and (hetero)arylamines. Enabled by diaryl-substituted 1,3-diketone ligands, the method exhibits broad functional group tolerance and streamlines the synthesis of pharmaceutically relevant arylethylamine scaffolds. The protocol is also applicable to propylene, nongaseous alkenes and 1,3-dienes, highlighting its utility for the conversion of petrochemical feedstocks into value-added products.

👉 For recent complementary work on ethylene difunctionalization, see J. Wu and co-workers' report on a ligand-modulated copper-catalyzed 1,2-dicarbofunctionalization of ethylene, here.

A. Pan, X. Song, W. Li, Y. Dong, Y. Pan, S. Zhang, S. Tang, S. Jin, W. Lin & H. Zheng*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c08589)

The authors report a tricationic xanthylium-based organophotoredox catalyst that enables primary O-benzoylhydroxylamines to act as bifunctional reagents in the oxyamination of alkenes. The method provides direct and regioselective access to 1,2-amino alcohols bearing secondary alkylamine motifs under mild conditions and exhibits broad substrate scope and functional-group tolerance. The transformation is regiocomplementary to the Sharpless aminohydroxylation and has been applied to the concise synthesis of natural products.

👉 For recent complementary work, see F. Wang and co-workers' iron-catalyzed asymmetric aminohydroxylation of alkenes using O-carbonyl hydroxylammonium triflates as bifunctional reagents, here.

A. V. S. Moyeda & D. H. Trauner*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06878)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15001557/v1) 🔓

The authors report a concise 12-step synthesis of the alkaloid stephadiamine. The carbocyclic framework was assembled through a homoconjugate addition–Wittig olefination cascade (“Schweizer–Fuchs annulation”), while a Wenker-inspired S_N2′ amination enabled construction of the aza[4.3.3]propellane core. A late-stage diastereoselective Strecker reaction established the characteristic syn-diamine motif.

R. Guo,^† F. Li,^† L. Wang,^† M. Ba, Z. Guo, W. He* & A. Li*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c02105)

The authors report a scalable 13-step synthesis of scholarisine A enabled by a reaction-altering biomimetic strategy that replaces a proposed biogenetic aldol cyclization with an MHAT-mediated radical cyclization. The approach provides efficient access to the scholarisine A alkaloid family, including scholarisines I, T, and W. Biological studies identified scholarisine I as an inhibitor of late-stage autophagy in cancer cells through impairment of lysosomal degradative capacity.

V. Ciccone, E. Lin, C. N. Prieto Kullmer, D. W. C. MacMillan & R. E. McNamee*

ACS Catal. 2026, ASAP (DOI: 10.1021/acscatal.6c02684) 🔓

The authors report a photoredox-catalyzed double deoxygenative fragment coupling of alcohols and carboxylic acids to access diverse, sp³-rich ketone scaffolds from abundant starting materials. The transformation proceeds under mild conditions and is further extended through a bis-radical SOMO stitching strategy that enables the coupling of two alcohol-derived fragments to furnish C1-connected ketones.

H.-J. Ai & S. L. Buchwald*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15005217/v1) 🔓

The authors report a silane-enabled catalyst-reactivation strategy that mitigates catalyst deactivation in copper-catalyzed C–N bond formation under air. By reducing off-cycle Cu(II) species, the method preserves the catalytically active Cu(I) species and enables amination, amidation, sulfonamidation, and N-heterocycle arylation reactions to be performed without gloveboxes, Schlenk techniques or degassed solvents.

Y. Xu,^† P.-P. Xie,^† K. Chen, P. Liu* & G. Dong*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15005200/v1) 🔓

The authors report an Ir-catalyzed, chemoselective aromatization of carboxylated cyclohexanes that uses carboxylic acids as traceless multifunctional anchors. The redox-neutral transfer dehydrogenation strategy enables the conversion of saturated cyclohexane precursors into substituted arenes with excellent chemoselectivity, even in the presence of cyclohexenes and cyclohexanones. Applications to the modular, late-stage synthesis of multisubstituted arenes highlight the utility of the approach.

J. A. Buldt, M. M. Belsuzarri, A. H. Patel, Y. Kraemer, T. Vu, R. Banerjee, J. A. Olvera, D. Tantillo*, L. M. Holder* & C. R. Pitts*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15004989/v1) 🔓

The authors investigate hybrid bioisosteric replacements as a strategy to balance the physicochemical effects of individual bioisosteres and validate SF₅-substituted bicyclopentanes (SF₅–BCPs) and SF₅–[2]staffanes as new hybrid bioisostere motifs. Scalable synthetic routes to versatile building blocks enabled their incorporation into drug-like molecules and systematic evaluation through structural, physicochemical, and in vitro ADME studies. The work establishes SF₅–BCPs and SF₅–[2]staffanes as practical motifs for tuning molecular properties in medicinal chemistry.

Honourable mention: Check out this updated study by E. Romero and co-workers on the bench stability of B₂pin₂. The authors demonstrate that trace impurities can initiate an autocatalytic solid-state decomposition process and provide practical recommendations for the storage and handling of the widely used diboron reagent.

🕹 Red Planet, Green Future. Nature has released an interactive game developed in consultation with scientists (don’t worry, it’s actually quite fun) that puts you in charge of turning the Red Planet into a habitable world.

Starting with a frozen planet averaging around −70 °C, you'll face a series of decisions that mirror real scientific debates: How do you warm an entire planet? Where should you source and store water? How do you deal with toxic Martian soil? What's the best way to start farming? Can you create an atmosphere humans could actually breathe?

Each choice affects your mission score and dramatically changes the projected timeline of your terraforming effort. Some solutions sound straight out of science fiction (nukes), while others are based on ideas that scientists are actively exploring today (Martian microorganisms). Give it a try and see whether your Mars becomes a thriving green world or remains a frozen wasteland.