U. Vezonik,^† G. Iannelli,^† D. Kaiser & N. Maulide*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02178-7) 🔓

The authors present a strategy for the peripheral modification of secondary N-methylamines that complements existing approaches while tolerating a broad range of functional groups and native amine substrates. The method is well suited to late-stage functionalization, enabling the direct bioconjugation of fully functionalized, unprotected building blocks and complex peptides. Its retrosynthetic flexibility also facilitates the single-step preparation of several commercially important pharmaceuticals.

H. Ji,^† J. Zang^† & H. Lu*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c08290)

The authors report a general strategy for single-carbon insertion into primary aliphatic amines. The transformation proceeds through deaminative carbon–carbon bond formation with oxime acceptors to furnish synthetically versatile oxime products, which can be readily converted into homologated amines and other carbon frameworks. The method exhibits broad functional-group tolerance, accommodates primary, secondary and tertiary alkyl-substituted amines, and is applicable to iterative homologation and the late-stage modification of bioactive molecules.

D. Moser, J. Hamm, C. M. Gampe & F. Schoenebeck*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c09918)

The authors report a general strategy for the direct N-adamantylation of structurally complex pyridines. The operationally simple method is also applicable to a range of N-heterocycles, including pyrimidines, pyrazines, quinoxalines and quinazolines, and accommodates alkyl groups that are inaccessible via conventional carbocation-based N-alkylation. Subsequent dearomatization provides access to N-alkyl piperidines. Evaluation of these previously inaccessible compounds revealed favourable in vitro ADME properties, including adequate solubility, permeability and metabolic stability.

J. Das,^† X. Zhang,^† Y. Tan, M. Abdelalim, T. Lu, C. Mauro, C. J. Regan & T. Cernak*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05959) 🔓

The authors report a dataset of more than 50,000 systematically varied C–N coupling reactions spanning palladium-, nickel- and copper-catalyzed conditions. Analysis of the dataset identified ligands that exhibit generalized performance across multiple metals and revealed previously overlooked mechanistic complexity, including background reactivity and aryne-mediated pathways operating under common coupling conditions.

Y.-F. Zhong, H. Xu, S.-X. Tang, Z.-Y. Jia, P.-P. Yang, Z. Mo, Y. Dang* & F. Wang*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c07489)

The authors report an iron-catalyzed enantioselective aminohydroxylation of alkenes enabled by newly developed N-Aryl-BIP ligands. The transformation employs O-carbonyl hydroxylammonium triflates as bifunctional reagents and provides access to a diverse range of β-amino alcohols from vinyl (hetero)arenes and 1,1-disubstituted alkenes in good yields and with high enantioselectivity.

J. Ke, R. Zhang, C. Du, H. Qiao, C. Wang, X. Liu, M. Pan & Z. Lu*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05648)

The authors report the first total synthesis of the 19-carbon picrotoxane terpenoid picrodendrin L. A highly functionalized cis-bicyclo[4.3.0]nonane core was constructed through a Danheiser cyclopentene synthesis, while the bridged lactone and spirolactone motifs were assembled through oxidation and halolactonization strategies, providing access to a previously unsynthesized subclass of picrotoxane terpenoids.

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

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.7155694)

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

Since 1947, the Balz–Schiemann reaction has remained the most widely used method for the synthesis of meta-fluoropyridines. However, the process relies on hazardous pyridyl diazonium salts and has been associated with numerous documented explosions, including incidents reported as recently as 2020. Here, the authors develop a safe alternative route to meta-fluoropyridines based on a shelf-stable reagent.

N. Lee,^† W. Wu,^† P. Schoch, D. K. Brownsey, J. Kristek, M. D. Wodrich & J. Waser*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15004944/v1) 🔓

The authors report the design and synthesis of novel hypervalent iodine(III) reagents bearing a bicyclo[1.1.0]butane (BCB) motif that act as BCB cation synthons. The reagents enable the first late-stage functionalization of the BCB core with sulfur- and carbon-centered nucleophiles, offering a complementary strategy to existing nucleophilic BCB chemistry and providing streamlined access to functionalized 1,3-disubstituted BCB building blocks.

F. E. Kidd, C. V. T. Vera & J. S. Bandar*

Chem. Sci. 2026, Accepted (DOI: 10.1039/D6SC02461K) 🔓

The authors report a base-promoted protocol for the direct oxidative coupling of amide α-C–H bonds with O-, S- and N-nucleophiles. The transformation proceeds through a deprotonation/halogenation/substitution sequence enabled by inexpensive 2-bromothiophenes as halogen oxidants and provides direct access to α-substituted amides. This strategy offers a streamlined alternative to conventional multistep syntheses that require preassembled α-functionalized carboxylic acid building blocks.

J. Justicia & S. P. Morcillo*

Chem. Soc. Rev. 2026, Tutorial Review (DOI: 10.1039/D5CS01539A) 🔓

This Tutorial Review examines how unstrained cyclic scaffolds can be selectively remodelled through radical-promoted C–C and C–N bond cleavage. Rather than cataloguing reactions, the authors present a unified framework in which skeletal editing is enabled by strategically installed radical gateways and controlled fragmentation pathways. Particular emphasis is placed on alcohol- and ketone-derived intermediates, the activation modes used to access them, and the divergent fates of the resulting radicals, including ring opening, contraction, expansion and functionalisation.

E. Moriya & J. Yamaguchi*

Chem. Soc. Rev. 2026, Review (DOI: 10.1039/D6CS00145A) 🔓

Functional group translocation has emerged as a powerful molecular editing strategy for accessing positional isomers from common precursors. In this Review, the authors define the conceptual boundaries of the field and provide a framework for understanding translocation reactions according to scaffold type, functional group identity and migration distance. They survey recent advances enabled by transition metal catalysis, photoredox activation and radical relay processes, while highlighting persistent challenges in selectivity, migration control and applications to complex molecules.

🇬🇧 🤝 🇪🇺 Re-forming the Bond. On 23 June 2016, the UK narrowly voted (52% to 48%) to leave the European Union. Fast forward ten years, six prime ministers, three general elections, and a global pandemic, and there are finally signs that UK science is beginning to rebuild its connections with Europe.

Following the UK's reassociation with Horizon Europe (the EU's €95 billion flagship research and innovation funding programme) in 2024, the UK's share of EU research funding rebounded from 5.8% in 2023 to 9.3% in 2024, although this remains well below the pre-Brexit peak of 16% in 2015.

The UK is also set to rejoin Erasmus+ in 2027, restoring opportunities for student and researcher exchanges but rebuilding scientific networks and influence may take considerably longer. This comes at a challenging time for UK science, with recent economic analyses suggesting Brexit has reduced UK GDP per capita by 6–8%, while high-profile setbacks—including MSD's decision to cancel its £1 billion London Discovery Centre—have fuelled concerns about the UK's competitiveness as a destination for research and innovation.