Note: Many of you will have noticed the recent ACS (and RSC) website updates, which have prompted considerable discussion. If you haven’t seen the changes yet, take a look at the JACS ASAPs page as an example: graphical abstracts, article views and Altmetric indicators are no longer as prominent or removed entirely, producing a browsing experience that feels considerably less efficient.

The previous ACS platform was a great example of a user-focused experience, allowing researchers to quickly scan new papers and use graphical abstracts to identify interesting and unexpected work beyond what a title alone might reveal. The new interface feels more like a journal that stopped publishing decades ago: a place to archive papers, rather than a tool designed to help us discover them.

Unfortunately, this may introduce additional friction for literature discovery. However, we will continue adapting our workflows to ensure Synthesis Spotlight remains a reliable way to navigate the ever-growing scientific literature.

M. Puriņš, J. Hwang & M. D. Levin*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10015)

The authors report sulfilimines as practical, photoactivatable nitrene precursors for C-to-N skeletal editing. Across three distinct C-to-N transmutation reactions, these safer alternatives to azides deliver comparable or improved efficiency with shorter reaction times and improved scalability. Readily prepared from diverse functional handles, including those installed by C–H functionalization, the precursors enable C-to-N replacement in complex scaffolds.

Z. P. Shultz, A. Lee-Sam, Y.-P. Chang, L. Sun, D. Grassie, A. Gabellini, K. Pedretty, T. Scattolin, V. Izumi, B. Fang, S. Sansil, R. Kakumanu, L. Wojtas, J. Koomen, E. Schönbrunn, A. Monastyrskyi, D. Duckett & J. M. Lopchuk*

Science 2026, 393, 408–416 (DOI: 10.1126/science.adx7219)

The authors report a modular sulfur(IV)-based reagent platform for the mild, late-stage installation of strain-release sulfonyl- and sulfonimidoyl-bicyclobutane motifs. This strategy enables bioisosteric replacement of acrylamide warheads while preserving the parent pharmacophore, providing sulfur(VI) covalent reactive groups with tunable strain-release reactivity and high cysteine selectivity. Incorporation into FDA-approved covalent inhibitors maintained cellular activity while improving proteome-wide selectivity relative to their acrylamide counterparts, with selected analogues demonstrating favourable pharmacokinetics and efficacy in preclinical mouse models.

👉 Science write-up, here.

S. Wang, D. A. Cagan, J. Tsien, J. Zhang, T. Gogula, A. V. R. Murthy, S. K. Nangunoori, G. Boga, M. S. Oderinde, A. M. Turner, H. C. Hang, Y. Kawamata* & P. S. Baran*

Nat. Chem. 2026 (DOI: 10.1038/s41557-026-02212-8)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15000647/v1) 🔓

The authors report a unified platform for the divergent synthesis of alkyl sulfur(VI) derivatives from abundant, unactivated feedstocks including ketones, alcohols, amines, and structurally complex molecules. This strategy employs alkyl hydrazines (or their sulfonylated derivatives) as practical radical precursors, which undergo simple thermal activation to generate alkyl radicals under mild conditions without photocatalysts or transition-metal catalysts. The broad functional-group tolerance of the approach is demonstrated through the synthesis of >70 sulfur-containing molecules, including direct functionalisation of complex natural products without protecting-group chemistry.

Y. Wang, Y. Jiang, W. Qi & Y. Qiu*

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01128-y)

The authors report an electrochemical nickel-catalysed doubly dehydroxylative cross-coupling of alkyl alcohols, enabling the direct formation of C(sp³)–C(sp³) bonds without prior alcohol prefunctionalization. The method exhibits broad functional-group tolerance and is well suited to the late-stage modification of hydroxyl-containing bioactive molecules.

W.-C. C. Lee,^† Y. Wang,^† A. J. Ressler^† & S. Lin*

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01112-6)

The authors review recent advances in electrochemical cross-electrophile coupling (eXEC) for C–X and X–X bond formation. The Review highlights emerging synthetic strategies, reaction development and catalytic systems across heteroatom bond-forming processes, while discussing current challenges and opportunities, including expanding electrophile scope, improving selectivity, enabling scalable reactions and developing new catalytic approaches.

A. D. Matthews, J. R. Lorenz & Z. K. Wickens*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c08262) 🔓

The authors report a new synthetic protocol for azole alkylation using alkenylthianthrenium electrophiles. The strategy proceeds through 1,2-azolothianthrenium intermediates followed by selective sulfonium excision via single electron transfer (SET), enabling a formal Markovnikov hydroazolation of readily available alkenes. The resulting radical intermediates can also be diverted beyond hydrogen atom transfer, providing access to challenging carboazolation products. Mechanistic studies reveal that a silyl radical-mediated activation of DMF generates a strong SET reductant in situ, enabling mild reductive activation of alkylthianthrenium electrophiles.

V. N. Nguyen, G. A. Hoteling, M. D. Delost, K. L. Constantini, W. B. Hughes, R. S. Paton & J. S. Bandar*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c09674) 🔓

The authors report a base-promoted method for direct benzylic C–H amination of alkyl(hetero)arenes using novel benzofuran- and indole-based halogen-transfer reagents. The approach enables coupling with anilines and, through the dual role of hexamethyldisilazide (HMDS) reagents as both bases and ammonia surrogates, provides access to primary benzyl amines. Guided by C–H acidity trends, this strategy enables amination across a broad substrate scope, including polyalkylarenes, hard-to-oxidize substrates, and oxidation-sensitive molecules that are challenging for conventional metalation, radical or nitrene-based approaches.

D. Jung,^† J. Y. Park,^† J. U. Kim,^† S. Kim, D. Lee & S. Lee*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c07828)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15002195/v1) 🔓

The authors report a photoredox-enabled catalytic transamination strategy enabling direct amine-to-amine interconversion without prefunctionalization. The reaction proceeds via polarity inversion, generating an electrophilic iminium intermediate that couples with a second amine nucleophile. Mechanistic studies support the involvement of α-amino radical and iminium intermediates, revealing two key principles governing selectivity: reaction directionality is controlled by relative nucleophilicity, while site-selectivity in C(sp³)–N bond cleavage is dictated by electronic activation or steric accessibility.

R. J. Martinez, D. Garg, L. R. Harrison, A. J. Rago, J. M. Young, M. G. Chavez, E. A. Voight & C. Uyeda*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05240)

The authors report a catalytic asymmetric cyclopropanation using chloroform as a methylidyne equivalent, providing a practical alternative to traditional carbene-based methods. The reaction affords enantioenriched metallocyclopropanes that undergo one-pot diversification to access a broad range of substituted cyclopropanes with high enantio- and cis-diastereoselectivity. The method enables rapid synthesis of stereochemically complex, sp³-rich cyclopropanes, including pharmaceutically relevant 1,2-diarylcyclopropanes.

H. Han, X. Tao, H. Noh, J. Jeong, C. Jung, J. Park & S. Hong*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10864)

The authors report a carbon-retentive skeletal editing strategy for the regioselective synthesis of pyrazoles from pyridines. Mechanistically divergent photochemical radical rearrangement and thermal polar cyclisation provide complementary substitution patterns, enabling access to densely functionalised pyrazoles from a common pyridine precursor. Both methods operate under mild, one-pot conditions and tolerate complex pharmaceutical scaffolds.

C. Etling,^† M. DiCairano^† & D. H. Trauner*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c09322)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15002882/v1) 🔓

The authors report the first total synthesis of the atypical diterpene alkaloid thelepogine, featuring a copper(I)-catalysed (4+1) cycloaddition of an amino enyne to construct the unusual pyrrolizine moiety. The route also features a 2,3-Wittig–Still rearrangement of a tetrasubstituted allylic alcohol to install two adjacent quaternary stereocentres, while a Beckmann-type rearrangement enables formation of the α-tertiary amine. This synthesis provides the first full spectroscopic characterisation of thelepogine, which was previously characterised only through X-ray analysis of a derivative.

N. Luo, M. Turberg, N. Tsuji, M. Leutzsch, S. Brunen & B. List*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c08353) 🔓

The authors report a general catalytic asymmetric cationic cyclization of geranyl derivatives using confined chiral imidodiphosphorimidate (IDPi) Brønsted acids and fluorinated alcohol additives. The reaction proceeds under mild conditions with high regio- and enantioselectivity across a broad range of substrates, providing access to cyclogeranyl scaffolds found in fragrance compounds, retinal precursors, and polycyclic terpenes, while also enabling selective squalene cyclization.

N. Hadler, E. Ramirez, M. Avaylon, M. Elkin, N. I. Rinehart, M. W. Mahoney, G. H. Weber, J. Hoche, J. G. Brandenburg, T. Perciano* & J. F. Hartwig*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c07313)

The authors report machine-learning models for predicting the enantioselectivity of ketone hydrogenation with Noyori-type diphosphine–diamine catalysts. Trained on literature data and >1,000 high-throughput experimental examples, 3D graph neural networks based on enantiodetermining transition-state structures outperform 2D graph, fingerprint and semiempirical quantum descriptor-based models. The approach enables accurate extrapolation to previously unseen catalysts and substrates.

C.-Y. Cai, Y. Kanda & T. Qin*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.9109858) 🔓

The authors report a three-component assembly strategy for the modular synthesis of hindered α-tertiary alkylamines from readily available ketones, amines and alkyltrifluoroborates. The method exploits the dual role of catechol as a reductant for ketiminium intermediates and an activator of organoboron reagents for alkyl radical generation. This approach provides broad access to α-tertiary amines with excellent functional-group tolerance, including challenging architectures such as consecutive quaternary centers, vicinal aminoether and diamine motifs.

🦖 $1.3 Million per Foot. One of the largest and most complete Tyrannosaurus rex skeletons ever discovered has just become the most expensive fossil ever sold, fetching $50 million at a recent Sotheby's auction in New York. Nicknamed Gus after the late Gary "Gus" Licking, owner of the South Dakota land where it was discovered, the 67-million-year-old T. rex measured 11.5 metres (38 feet) long and stood 3.8 metres (12.5 feet) tall. The fossil comprises 183 bones, including 30 of 32 rarely preserved belly ribs, representing 61% of the skeleton by bone count and an estimated 75–80% of its total bone mass.

Around 82% of the skull remains intact, while bite marks to the skull and jaw, together with healed fractures in several ribs, suggest Gus survived violent encounters with other tyrannosaurs before dying. Such exceptional preservation provides rare insights into the life of an animal that lived 67 million years ago.

The sale surpassed the previous auction record of $44.6 million set by the stegosaur Apex in 2024 (now on loan to the American Museum of Natural History) and has reignited debate among palaeontologists. Unlike many countries, where fossils are considered state property, US law generally permits fossils discovered on private land to be bought and sold. While this system incentivises commercial palaeontologists to spend years—and millions of dollars—recovering specimens that might otherwise remain buried or erode away, critics argue it can also place scientifically important fossils beyond the reach of museums, researchers and the general public.