Editor’s Note: Last week, Microsoft Defender incorrectly identified links in the newsletter as potentially unsafe, resulting in Outlook users being unable to access the papers for around 12 hours, beginning approximately 24 hours after the newsletter was sent. The problem has since been resolved and all links are now working normally. However, I’ll be monitoring this closely and if the warning reappears, I’ll report it directly to Microsoft for review. If you experience any issues at all, feel free to hit reply to let me know, and I’ll look into it promptly.

Also, a quick thank you to everyone who engaged with Knight Chemicals in last week’s issue! It’s been great to hear positive feedback from readers who have used them before, as well as from others who are keen to try the sulfonyl hydrazides!

A. G. Feng, S. Wu, E. Palomo & R. R. Knowles*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c16630) 🔓

The authors report a light-driven Wolff–Kishner reduction of aryl and aliphatic carbonyls at near-ambient temperature under essentially neutral conditions. By harnessing light energy to overcome the thermodynamic barriers of the classical reaction, the method avoids the strong base and high temperatures typically required, overcoming key limitations of traditional Wolff–Kishner chemistry, including ester and amide hydrolysis, and α-carbonyl epimerization.

D. Behera,^† S. Chatterjee,^† Á. Adorján, C. Wang, A. Altun, F. Neese & T. Ritter*

Nature 2026 (DOI: 10.1038/s41586-026-11108-z) 🔓

The authors report alkylthianthrenium salts as versatile carbene donors that enable cyclopropanation with diverse olefin and carbene partners. The low Lewis basicity and steric shielding of thianthrene facilitate efficient carbene transfer to iron, enabling cyclopropanation of unactivated 1,2-disubstituted and trisubstituted alkenes with broad functional-group tolerance. The salts also offer a favourable safety profile, enabling scale-up and ball-milling, while Cu catalysis extends the method to challenging internal alkenes. Beyond cyclopropanation, thianthrenium ylides also enable σ-bond insertion and sigmatropic rearrangements.

👉 C&EN write-up, here.

P.-F. Zhong, C. Yang, L. Guo* & W. Xia*

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01162-w)

The authors report a photoelectrochemical Fe–Ni dual-catalytic platform for selective C(sp³)–C(sp³) cross-coupling directly from native carboxylic acids, alcohols, and aldehydes. The method enables double decarboxylative, dehydroxymethylative, and deformylative couplings across primary, secondary, and sterically hindered tertiary carbon centres without pre-activation. Mechanistic studies support a Ni(II)/Ni(III)-catalysed S_H2 pathway involving radical sorting.

A. R. Bena, T. Banik,^‡ C. Giannoudis,^‡ F. Ortis,^‡ D. Bím, H. Baunis, G. H. Palissery & B. Pieber*

Nat. Catal. 2026 (DOI: 10.1038/s41929-026-01616-6) 🔓

The authors report a mechanistically guided ligand design that enables Ni(I)-catalysed C(sp²)–heteroatom coupling of electron-rich aryl bromides with N-, O-, S- and P-based nucleophiles. A tailored ligand overcomes the poor oxidative addition reactivity that has limited Ni(I)/Ni(III) catalysis, while a non-nucleophilic base enables direct visible-light generation of Ni(I) from a bench-stable Ni(II) precatalyst. The method operates at nickel loadings as low as 100 ppm and tolerates sterically encumbered nucleophiles, enabling gram-scale synthesis and late-stage functionalisation of complex molecules.

I. E. Petrucci, J. Masson-Makdissi, Z. Xue, C. McCleary, M. P. Glogowski & M. D. Levin*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c13570)

The authors report three aliphatic skeletal transmutations of heteroaryl-fused piperidines via interrupted nitrogen deletion, generating dearomatized vinylcyclopropanes that serve as versatile 5-carbon synthons. These undergo Rh-catalysed carbonylation, polar ring-opening, or photochemical radical cyclization to deliver cyclohexanones, dihydropyrans, and thianes, respectively. Computationally determined dearomatization penalties predict the propensity for productive vinylcyclopropane formation across different heteroaryl substrates.

M. Georg, Y.-D. Kwon, M. Boeckle, D. Yang, D. H. Ess & L. Kürti*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14811) 🔓

The authors report a direct single-step oxidation of primary amines to electrophilic N-alkyl-O-mesyl hydroxylamines using dimesyl peroxide, providing readily accessible reagents for electrophilic amination. The mild transformation tolerates structurally complex and chiral amines, including amino acid, natural-product, and pharmaceutical derivatives. The resulting reagents enable C–H amination, olefin aziridination, and aza-Rubottom oxidation protocols.

Y. Nam, A. T. Tam, D. N. Rojas, T. E. Reynolds, J. A. Brekan, S. Sil & K. A. Scheidt*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c10893)

The authors report the evolution of a total synthesis strategy that ultimately resolved the long-standing structural ambiguity of secalosides A and B. A late-stage ring contraction of a 13-membered bis-lactone formed both the highly strained 10-membered bis-lactone and the configurationally correct indane core via an unusual transannular oxidative enolate coupling. Synthesis of the two proposed diastereomers followed by spectroscopic comparison with natural samples established the (1S,2S,3R) configuration of the secalosides.

W. Zhao, J. Zhen & M. Dai*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c15246) 🔓

The authors report an enantioselective total synthesis of (−)-methyl gummiferolate, a complex diterpene natural product with a tetracyclic ent-atisane core, in 18 steps. Pattern recognition analysis traced the core to chiral pool (S)-perillaldehyde and a six-membered ring starting material accessible via an enantioselective Rawal diene Diels–Alder reaction. A substrate-controlled MHAT-initiated Baran reductive olefin cross-coupling forged the six-membered B ring through a stereoselective 6-endo-trig radical cyclization, while intramolecular alkylation constructed the challenging bicyclo[2.2.2]octane subunit.

Z.-Q. Xue, F.-S. Jiang, W.-K. Ge, J.-B. Sun, Z.-X. Gao, M.-Z. Zhu, L.-F. Hu, Y. Zong, R. Tong, H.-X. Lou* & Z.-J. Xu*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14997)

The authors report divergent asymmetric total syntheses of miophytocen D, roridin E, verrucarin J, and verrucarol. An exo-selective Diels–Alder cycloaddition rapidly assembles the conserved tetracyclic trichothecene core, while biomimetic oxacyclization forges the sterically congested tetrahydropyran ring. Conformation-controlled alkene–epoxy cyclization enables divergent skeletal diversification, while modular RCM provides access to macrocyclic trichothecenes. The approach delivers the first total synthesis of miophytocen D and a hundred milligram-scale synthesis of verrucarol.

Y. Xu,^† Z.-Z. Pan^† & G. Dong*

ACS Catal. 2026, ASAP (DOI: 10.1021/acscatal.6c05353)

The authors report an Ir-catalysed alkene translocation that directly converts electrophilic α,β-unsaturated amides into nucleophilic enamides by shifting the C=C bond across the amide linkage. The redox-neutral transfer hydrogenation proceeds without a strong base and tolerates diverse functional groups. Mechanistic studies support an irreversible intramolecular hydrogen transfer pathway, and preliminary results demonstrate enantioselective transfer hydrogenation.

S. Kaydos-Daniels, Z. F. Murphy, E. C. Vik & N. B. Bissonnette*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15009611/v1) 🔓

The authors report an iron-mediated MHAT hydrosulfinamidation of unactivated olefins that converts readily available alkenes into Markovnikov sulfinamides. The room temperature, irradiation-free process uses inexpensive reagents and tolerates diverse functional groups, including complex terpenes, steroids, and pharmaceutical scaffolds. The method was demonstrated on >20 gram scale using standard laboratory glassware.

🍀 It's Not Easy Being Green. An analysis of 1.3 million reactions spanning 40 years of US patent data has found that hazardous solvents remain stubbornly prevalent. Starting in 1976, solvents classified as hazardous were used in around 60% of patented reactions. By 2016, that figure had risen to more than 70%, despite decades of green chemistry.

Many of the patents analysed relate to exploratory research early in the drug discovery pipeline, where speed and precedent matter. When the ‘make’ phase of a DMTA cycle is already the bottleneck, there is enormous pressure to make compounds quickly and reliably. That favours workhorse solvents that dissolve various substrates, tolerate diverse reagents, work across a range of temperatures, and fit readily into high-throughput and automated workflows. If a reaction in DMF can get you to the final product, there is little incentive to spend days trying to make the same chemistry work in a greener solvent—especially in medicinal chemistry where the job is to deliver compounds, not develop a new solvent system. That lack of incentive is echoed by David Leahy, chair of the ACS Green Chemistry Institute advisory board, who says there is “almost zero incentive for the discovery chemist to make these molecules with more environmentally friendly conditions.”

Even when regulations force chemists to abandon a hazardous solvent, the study found that they often swap one problematic solvent for another rather than adopting a greener alternative. Dichloromethane use has actually increased, while rising trifluoroacetic acid consumption raises additional concerns around PFAS. Another problem is that reaction-planning models are trained on historical literature and patent data, meaning they can inherit the solvent choices of previous generations. Without explicit sustainability criteria, AI could simply become very good at recommending the solvents we already use.

To help break that cycle, the researchers created Solvent Explorer, an interactive companion to the study. You can explore solvent use across the 1.3 million reactions to see how solvent choices have changed over time, and investigate greener alternatives for different transformations.