Note: Due to annual leave, next week’s issue will cover papers published from Monday 6^th July – Friday 10^th July, with papers published over the weekend included in the following week’s edition.

N. D. D’Arcy-Evans, G. Rossini, B. D. A. Shennan & D. J. Dixon*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c03051) 🔓

The authors report a general strategy for the direct dehomologation of secondary and tertiary lactams through formal α-methylene deletion. The one-pot protocol combines amide α-oxidation and oxidative decarboxylation to enable ring-size editing across a broad range of lactam scaffolds, including pharmaceutically relevant molecules. Applications to ring-size scanning, iterative ring contraction, and the synthesis of β-amino acid derivatives highlight the utility of the approach.

Z. Zhang & G. Dong*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10600)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15003770/v1) 🔓

The authors report reductive and annulative carbonyl-removal methods enabled by N′-alkyl hydrazonamide (NAHA) reagents, proceeding via sequential double C–C bond cleavage. These transformations convert diverse cyclic ketones into the corresponding ring-opened and ring-contracted analogues with broad functional-group tolerance. Applications to the late-stage modification of complex bioactive molecules, the synthesis of all-carbon quaternary centers and terminally deuterated motifs, and iterative ring contraction highlight the versatility of the strategy.

L. Yu,^† J. Zhang,^† X. Zhang,^† X. Wu,^† R. Liu, C. H. Au, H. Ogawa, R. Tong* & H. Nakamura*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05294) 🔓

The authors report a unified synthetic platform for the preparation of biaryl- and triaryl-bridged cyclic peptides inspired by ribosomally synthesized and post-translationally modified peptide (RiPP) architectures. Combining electrochemical decarboxylative C–C bond formation with Larock macrocyclization, the modular strategy enables the incorporation of ten distinct natural and artificial biaryl/triaryl linkages and provides streamlined access to fluorinated analogues and cyclic peptides spanning diverse ring sizes. The platform was applied to the synthesis of a large library of RiPP derivatives and several cihunamide analogues prepared using this approach exhibited antibacterial activity.

H. Lu,^† Y. Li,^† N. Ma,^† R. Chen, Y. Wang, M. Chen, W. Zhang, X. Wang, H. Jin, C. Ding, S. Chen,* A. Zhang* & Z. Fan*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06488)

The authors report a nickel-catalyzed, stereoselective C1-arylation of unprotected saccharides with (hetero)aryl bromides using glycosyl sulfonyl hydrazides as readily accessible glycosyl donors prepared in a single step from native sugars. Key to the transformation is the development of N,N′-disulfonylpyridinedicarboxamidine tridentate ligands, which enable high reactivity and anomeric selectivity. The method is applicable to a broad range of mono- and oligosaccharides, and its utility was demonstrated through the synthesis of a Taxol–sugar conjugate library, including analogues with improved aqueous solubility and selective anticancer activity.

👉 While several groups have recently reported complementary approaches to the synthesis of C-aryl glycosides using glycosyl sulfonyl hydrazides (too many to note here), readers are directed to the seminal study by Baran, Aggarwal and co-workers.

H. Chen, J. N. Mauro, M. C. Madhusudhanan, R. A. Madiu, A. Khosravi, S. Gulzar, G. Zhao, J. Chin, P. Liu* & M.-Y. Ngai*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10100)

The authors report a chiral ligand-modulated, nickel-catalyzed stereoselective radical migratory cross-coupling for the direct C2-arylation of carbohydrates from readily available 1-halosugars. Central to the strategy is a previously underexplored class of chiral 2-(aminomethyl)pyridine (Ampy) ligands, which enable catalyst-controlled stereoselectivity through nickel-mediated radical capture. The method accommodates a broad range of aryl boronic acids and carbohydrate substrates, providing streamlined access to stereodefined C2-aryl carbohydrates.

M. G. J. Doyle,* M. E. Jespersen, S. Noureen, Z. Chen, T. L. Jefferson, C. A. Baptista, M. Houot, J. J. C. Struijs, C. A. Goult, A. A. Bakulin, R. S. Paton, A.-J. Avestro* & V. Gouverneur*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c07703) 🔓

The authors report a photocatalytic, site-selective monohalodefluorination of perfluoroalkyl compounds using N-arylphenothiazine photocatalysts and simple halide salts, providing a modular platform for precise C–F functionalization. The transformation proceeds through an oxidative consecutive photoinduced electron transfer (conPET) manifold that enables net halogen exchange under mild conditions. This mechanistically distinct strategy provides efficient access to brominated and chlorinated perfluoroalkyl derivatives.

M. Lovell, S. Ortalli, R. Sánchez-Bento, M. Tredwell, J. Ford* & V. Gouverneur*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c09649) 🔓

The authors report a Ni-mediated ¹⁸F,D₂-monofluoromethylation of (hetero)arenes from aryl (pseudo)halides, enabling the late-stage installation of fluorine-18 and deuterium in a single step. By replacing conventional S_N2-based radiochemistry with a cross-coupling strategy, the method broadens substrate scope, improves precursor accessibility, and exhibits excellent functional group tolerance. Applications to complex bioactive molecules and the semiautomated synthesis of an ¹⁸F,D₂-labelled PARP radiotracer highlight the potential of the method.

P. Natho,^† A. Vicenti,^† M. Colella, F. Pasca, G. Romanazzi, M. Niso, C. Abate, E. Mesto, E. Schingaro & R. Luisi*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.3488479) 🔓

The authors report a modular synthesis of a new class of “super-strained” spirocyclic 1-azabicyclo[1.1.0]butanes through a Johnson–Corey–Chaykovsky reaction of four-membered-ring sulfonium salts with azirines. The scope, scalability and stability of the new scaffold are investigated, and its synthetic utility is demonstrated through strain-release functionalization to access highly functionalized 1-azaspiro[3.3]heptanes. AI-supported target fishing followed by in vitro radioligand binding studies further identified derivatives with promising affinity for the sigma-1 receptor.

J.-L. Fu, J.-Y. Wu, Q. Fan, J.-H. Xue, Q. Li & H. Wang*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.1809869)

The authors report a metal-free direct deaminative alkynylation of aliphatic primary amines using alkynyl bromides as coupling partners and an N-anomeric amide as the nitrogen-deletion reagent. The method enables C(sp³)–C(sp) bond formation without prior amine prefunctionalization and exhibits good functional-group tolerance across a range of aliphatic amines, including pharmaceutical- and natural product-derived substrates.

A. Ali, L. Kloene, J. Koedel, Y. Guo, M. Altia & R. M. Koenigs*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15005480/v1) 🔓

The authors report a catalyst-controlled nitrene transfer that enables divergent amination of bicyclobutanes. Rh(II) catalysis promotes selective strain-release amination to afford aminocyclobutenes, providing efficient access to cyclobutane amino acids through an amination–hydrogenation sequence. In contrast, photocatalytic nitrene activation induces double amination and skeletal remodeling to furnish dihydropyrrolidines, which are converted into substituted pyrroles.

L. Modell,^† J. C. Moore,^† S. O. Revely, K. D. Jones, S. P. Argent, Q. Lefebvre, L. Stirchler, C. Giorgiutti, C. H. de Moor & H. W. Lam*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv-2025-077c0/v2) 🔓

The authors report an enantioselective synthesis of 2,4-disubstituted homocubanes, establishing these scaffolds as readily functionalized, chiral meta-benzene bioisosteres. A versatile enol triflate intermediate enables late-stage diversification through well-established cross-coupling chemistry, providing streamlined access to (hetero)aryl-, alkynyl-, alkyl-, carbonyl-, and heteroatom-substituted homocubanes. Homocubane analogues of the anticancer drugs ponatinib and sonidegib revealed pronounced enantiomer-dependent differences in kinase inhibition and metabolic stability.

☕ Under Pressure. It's hard to imagine that one of the world's largest agricultural industries begins with a modest flowering plant. Yet the global coffee industry is worth more than $250 billion annually—roughly equivalent to New Zealand's entire economy. More than 2 billion cups are consumed every day, requiring around 10 million tonnes of beans each year. Remarkably, almost all of that supply depends on just two species, both of which are increasingly threatened by climate change.

A recent Nature feature explores how climate change is placing unprecedented pressure on coffee production. Arabica (Coffea arabica), prized for its flavour, struggles as temperatures rise, while robusta (Coffea canephora) is more heat tolerant but requires substantially more water. Beyond these two commercially dominant species lies an untapped resource: more than 130 wild Coffea species that collectively account for just 1% of global production.

With temperatures rising and droughts becoming more frequent, researchers are increasingly looking to this genetic diversity. In Ethiopia, the birthplace of arabica coffee, thousands of wild and cultivated coffee plants are being conserved in living collections to provide the genetic resources needed for breeding more climate-resilient varieties. Botanists are also revisiting lesser-known species such as C. stenophylla, whose beans reportedly rival premium arabica in flavour alongside the plant's remarkable tolerance to heat and drought.

Chemistry also has an important role to play. A single cup of coffee contains a complex mixture of more than 2,000 organic compounds, and scientists are working to understand how these molecules shape flavour and aroma. Researchers are also exploring how grinding conditions, moisture content and brewing pressure influence extraction efficiency, aiming to maximise flavour while reducing the amount of coffee required per cup.