Z. Zhang & G. Dong*

ChemRxiv 2026 (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. The strategy enables late-stage modification of complex bioactive molecules and provides access to all-carbon quaternary centers, terminally deuterated motifs and iterative ring-contracted scaffolds.

Y.-B. Wang, Y.-A. Xu, C. Li, G.-Y. Cheng, S.-H. Xiang & B. Tan*

Science 2026, 392, 850–857 (DOI: 10.1126/science.aeb8506)

A relay energy transfer catalytic mode was developed to overcome the energy transfer barrier caused by catalyst-mediated spatial separation in asymmetric photocatalysis. Chiral energy transfer acid catalysts with high triplet energies were designed to bridge energy transfer between the photosensitizer and substrate, eliminating the stoichiometric requirement for acid activators in the dearomative [4+2] cyclization of quinolines and alkenes. Fine-tuning of the catalyst side arms and the proximity of the catalytic site to the chiral source enabled high regio-, diastereo- and enantioselectivity.

A. Nikbakht,^† X. Li,^† J. Wan, C. Qin & A. H. Hoveyda*

Science 2026 (DOI: 10.1126/science.aee3540)

The authors report a programmable strategy for skeletal remodeling of macrocycles, enabling systematic modification of ring size and structure from a common diene or macrocyclic olefin “hub”. A small set of catalytic transformations allows iterative ring expansion, contraction and functionalisation under mild conditions. The approach provides streamlined access to diverse macrocyclic analogues, exemplified by the synthesis of 14 epothilone C derivatives in an average of three steps per analogue. This platform offers a practical alternative to de novo synthesis for exploring macrocycle structure–activity relationships.

L.-W. Fan,^† L. Qin,^† C.-Y. Xiao,^† J.-B. Tang,^† H. Lv, Q. Song, F. Liu, J.-P. Wang, Y.-S. Zhang, D.-L. Yuan, J.-Q. Bian, Q.-S. Gu* & X.-Y. Liu*

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01091-8)

The authors report an enantioselective radical S–C cross-coupling strategy for the synthesis of sulfur-stereogenic alkyl sulfilimines from unactivated C(sp³)–H bonds and N-acyl sulfenamides. Complementary photoinduced and thermal protocols enable the generation of alkyl radicals from primary, secondary and α-functionalized alkanes, delivering the corresponding products with high enantioselectivity. The method is applicable to gram-scale synthesis, downstream derivatization and late-stage functionalization of pharmaceutical scaffolds.

R. Al-Ahmad,^† I. M. de la Torre Roehl,^† C. Liu, R. Sarpong* & M. Dai*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c04423) 🔓

This Perspective examines the emerging role of single-atom skeletal editing in complex molecule synthesis. Drawing on historical examples and modern case studies, the authors illustrate how strategically encoded skeletal edits can streamline retrosynthetic design, enable access to challenging molecular frameworks, and overcome limitations in conventional reactivity. The discussion highlights current methodological gaps while advocating for new skeletal editing reactions and programmable synthetic strategies that treat molecular frameworks as editable architectures.

P. Spieß,^† M. Vavrík,^† J. Frey, U. Vezonik, D. Kaiser & N. Maulide*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c05299) 🔓

Despite notable progress in catalytic olefin isomerization for distal Csp³–H functionalization, most methods rely on complex metal-based catalytic systems and face challenges in achieving regiodivergent outcomes. Here, the authors present a conceptually distinct approach based on cationic olefin isomerization for regiodivergent Csp³–H functionalization, in which selectivity arises from a ketone-assisted process termed cation sampling. This platform enables site-selective functionalization of sp³-hybridized carbons, allowing access to γ- and δ-functionalized products through selective C–heteroatom bond formation at challenging positions.

C. Randolph, O. Buravov, Z. Grimm, P. K. Mykhailiuk* & L. Kürti*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06697) 🔓

The authors report a one-pot strategy for the de novo synthesis of highly substituted pyrroles from O-vinylhydroxylamines and activated alkynes. The transformation proceeds through an aza-Michael/oxaza-Cope rearrangement/aromatization cascade, generating versatile dihydropyrrole hemiaminal intermediates that can be converted directly to pyrroles or selectively functionalized. The method accommodates a broad range of substrates and provides streamlined access to pyrrole substitution patterns that previously required harsh conditions or hazardous acetylene-based methods.

S.-M. Guo, T. Hülße, C. G. Daniliuc, L. Kellermann, E. Horst & A. Studer*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c02798)

The authors report a visible-light-mediated intermolecular formal cycloaddition between oxazino pyridines and vinyl azides, providing efficient access to meta-alkylated pyridines, including key metyrapone analogues. The methodology features a broad substrate scope, one-pot compatibility and synthetic utility.

R. Li,^† C. Liu,^† W. Li,^† M. V. Truong, S. W. Khoo, Y. Li, R. R. Merchant, B. S. Matsuura, H. Y. J. Fung, S. Chen* & T. Qin*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c06952)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv.15001863/v1) 🔓

The authors report a family of chiral sulfonimidoyl radicals that enable stereoretentive radical transfer using bench-stable reagents. This modular approach provides switchable access to enantioenriched sulfoximines and sulfinamides while avoiding the use of strong oxidants and organometallic nucleophiles. Mechanistic and computational studies offer insight into the high stereochemical fidelity of these underexplored chiral sulfonimidoyl radical species.

R. L. Pilkington & D. L. Priebbenow*

ACS Catal. 2026, ASAP (DOI: 10.1021/acscatal.6c02259)

Previously: ChemRxiv (DOI: 10.26434/chemrxiv-2025-grgz8) 🔓

The authors report a photocatalytic strategy for dual functional-group transposition across linear alkyl frameworks through visible-light-induced decarboxylation of β-thioether and β-boryl carboxylic acids via the corresponding oxime esters. Radical S,N- and B,N-reconfiguration pathways enable the synthesis of diverse 1,2-iminosulfide and 1,2-iminoboronic ester products under energy-transfer photocatalysis. The resulting 1,2-imino-functionalized compounds are amenable to further synthetic elaboration.

Q. Shi & W. H. Liu*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.4999077)

The authors report a direct conversion of amides to alkenes using 9-BBN and a Cp₂ZrCl₂ precatalyst under mild conditions. Representing a third mode of amide derivatization beyond deoxygenative and deaminative pathways, the transformation enables efficient single-step access to hydrocarbons from readily available amides.

A. A. Kadam,^† K. Lee,^† Y. Liao, A. Knyazev, M. J. Lourenço, P. Tung, A. N. Cauley, J. M. Dones, M. S. Oderinde, J. Kempson & J. B. Roque*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003452/v1) 🔓

The authors describe a nickel-catalyzed migratory arylation of aliphatic amines using Katritzky salts enabled by a “store-and-release” strategy. In this approach, dihydropyridines serve as latent reservoirs for translocated alkyl radicals, decoupling chain walking from the cross-coupling cycle. The protocol enables regiodivergent deaminative arylation of Katritzky salts derived from diverse primary amines with a broad range of aryl and heteroaryl bromides, while exhibiting broad functional-group tolerance and compatibility with pharmaceutically relevant substrates.

Q. Zheng, G. Lin, V. Morlacci, L. Raineri, L. Liu, L. Capaldo* & T. Wan*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003501/v1) 🔓

The authors report a modular olefin cross-coupling strategy that enables tail-to-tail C(sp³)–C(sp³) bond formation from simple alkene feedstocks. The method combines in situ Brown hydroboration of unactivated alkenes with photocatalytic Giese-type addition, allowing direct engagement of linear organoboranes without intermediate isolation. The operationally simple protocol exhibits broad applicability and provides a practical platform for the rapid synthesis of sp³-rich molecules from olefins.

L. P. Pop & R. A. Shenvi*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003543/v1) 🔓

The authors report a synthetic approach to the species-selective succinate dehydrogenase (SDH) inhibitor siccanin that rapidly accesses its highly hindered cis-syn-cis drimane core and associated chemical space. The strategy addresses longstanding challenges in the synthesis of this scaffold, including stereocontrolled etherification and late-stage C15 oxidation. Computational studies were used to rationalize and predict conformational preferences, stereochemical outcomes and the reactivity of key O-centered radical intermediates, enabling the development of a concise route to siccanin.

X. Wang,^† J. Luo,^† B. Wang, T. Long, J. Li, Y. Xu, S. Zou, Q. Zeng, Y. Yin, X. Xu, T. Han, H. Wang, Z. Liu, L. Tao* & C. Li*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15003439/v1) 🔓

The authors report a scalable total synthesis of the polyether ionophores ecteinamycin and nonthmicin, featuring electrochemical decarboxylative alkenylation, an enzyme-catalyzed anti-Baldwin cyclization and a redox-economic asymmetric C–C bond formation. The synthesis enabled systematic biological evaluation, revealing that nonthmicin selectively suppresses Clostridioides difficile, protects mammalian cells from toxin B-induced cytopathology, and exhibits efficacy in a mouse model of Clostridioides difficile infection.

Y. Wei,^† K. Kasama,^† A. Igartua, D. B. Yildiz, A. Ceuninck, T. dos Santos, C. Büttner, D. Thevenet, M. Bossart, V. Derdau, M. Méndez, P. Jubault, T. Poisson,* B. Roure* & D. Leonori*

Chem. Sci. 2026, Accepted (DOI: 10.1039/D6SC03470E) 🔓

The authors report a photochemical strategy that directly converts pyrazoles into imidazoles with broad functional-group tolerance and complete retention of peripheral substitution. The reaction is effective across densely substituted and bicyclic systems, and extends to pyrazolo[1,5-a]azines, a previously inaccessible class of heterocycle reconfiguration substrates. The method is readily translated to continuous flow, highlighting its potential for scalable synthesis.

B. W. Dehnert, C. Leung & O. Kwon*

Org. Lett. 2026, ASAP (DOI: 10.1021/acs.orglett.6c01643)

The authors report cleavage of the C(sp³)–C(sp²) bonds of alkenes as a route for radical fluorination. In this process, ozone leads to the creation of α-methoxyhydroperoxide intermediates from alkenes, with subsequent treatment with Fe^II and Selectfluor providing a variety of alkyl fluorides. The products are obtained under mild, aerobic reaction conditions within short reaction times.

🥚 Scrambled, Poached, Fried… Artificial? Colossal Biosciences has unveiled an artificial egg system it says could support conservation breeding and future de-extinction efforts. The design combines a 3D-printed lattice shell with a transparent silicone membrane, alongside a viewing window that allows real-time monitoring of embryo development, including potential gene-editing effects.

The company claims ~26 chicks have hatched using the system. Longer-term, Colossal plans to revive extinct birds such as New Zealand’s South Island giant moa (Dinornis robustus). It’s reassuring that the inevitable Jurassic Park comparisons haven’t discouraged attempts to resurrect a three-metre-tall flightless giant whose name translates to “terrible bird”.

The work has only been shared via press release and video, with no peer-reviewed publication or preprint, limiting independent evaluation. Artificial egg systems are not new, but most have struggled with oxygen delivery and often require elevated oxygen levels that can stress embryos. Colossal claims its membrane enables development under normal atmospheric oxygen conditions.

The company, based in Dallas and co-founded by Ben Lamm and geneticist George Church, brands itself as the first “de-extinction and species preservation company”. Alongside its high-profile woolly mammoth programme, it has engineered a “woolly mouse” carrying mammoth-linked gene edits that produce a cold-adapted, shaggy coat — albeit with a distinct lack of tiny tusks — and is also pursuing passenger pigeon and thylacine revival efforts.