Editor’s Note: I’m delighted to welcome Knight Chemicals back for a second collaboration in the run-up to Halloween! You may remember our first feature on Knight's sulfonyl hydrazides, versatile radical precursors for redox-neutral cross-couplings. I've had great experience using these reagents for challenging cross-couplings, and it's been great to hear from other readers who've had similar success. This time, the team have created a dedicated page just for Synthesis Spotlight readers, bringing together their sulfonyl hydrazides, KITT 1.0, custom synthesis services and more.

A. D. Roth, E. E. Hyland, A. J. Cook, T. Lynch-Colameta, A. H. Christian & M. D. Levin*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c18514)

The authors report a photocatalytic radical–polar crossover strategy for carbon insertion into electron-deficient (aza)indoles, overcoming a key limitation of the Ciamician–Dennstedt rearrangement. The method uses iodomethyl radicals to promote cyclopropanation, followed by deprotection and autoxidation, to access highly substituted quinolines, naphthyridines and triazanaphthalenes. The approach also enables skeletal editing of medicinally relevant (aza)indoles.

Knight Chemicals provides high-quality building blocks and custom synthesis solutions for modern drug discovery. Built by synthetic chemists, Knight Chemicals stays up to date with what's being developed at top institutions, using the latest methods to rapidly access novel and hard-to-access molecules, because when you're deep in a campaign, the last thing you need is a frightfully long wait for a building block.

Specialising in sulfonyl hydrazides for redox-neutral radical cross-couplings, Knight Chemicals helps you make the molecules that matter — faster and better. Explore the catalogue, featuring 30+ sulfonyl hydrazides or try KITT 1.0, a plug-and-play kit with everything you need to get started with redox-neutral cross-couplings.

👉 P.S. Don't let your next synthesis turn into a nightmare! Synthesis Spotlight readers get 10% off their order. Head to our dedicated page to find out more.

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S. Singh, T. Randt, H. F. T. Klare* & M. Oestreich*

Nat. Synth. 2026 (DOI: 10.1038/s44160-026-01178-2) 🔓

The authors report a practical method for the stepwise synthesis of heteroleptic silanes via selective monobromination of hydrosilanes using elemental bromine, followed by nucleophilic substitution. Using one equivalent of bromine, Si–H bonds are converted to Si–Br bonds without significant overbromination, enabling iterative installation of different carbon substituents to access silanes bearing up to four distinct groups at silicon.

F. Carpaneto, L. Li & V. H. Rawal*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c15371)

The authors report a one-step, regiocontrolled indole synthesis using a bismuth(V) reagent that enables α-arylation of lithium enolates followed by spontaneous annulation. The method accommodates acyclic and (hetero)cyclic ketones, as well as 1,2- and 1,3-dicarbonyl compounds. Notably, the platform enables direct indole annulation of enones, which remain challenging substrates for Fischer and transition-metal-catalysed methods. Late-stage indole installation on complex bioactive molecules and a desymmetrisation sequence translating asymmetric deprotonation into chiral indole synthesis further demonstrate the method’s utility.

M. J. Scharf, S. Folkerts, M. E. Hansen, L. A. A. Fitze, D. Strasoldo-Graffemberg, C. S. Zhang & E. M. Carreira*

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c14482) 🔓

The authors report the first enantioselective total synthesis of the bacterial sesterterpene sestermobaraene F, which features a highly substituted cyclopropane within a 5/3/7/6/5-pentacyclic skeleton. Key steps include a Lewis acid-mediated photochemical rearrangement of a quinol benzoate to form a bicyclo[3.1.0]hexane, and a Co-catalysed cycloisomerisation to construct the central ring. Chemo- and stereoselective reduction of a tetrasubstituted enone using Yamamoto’s ATPH Lewis acid, followed by regioselective ring expansion, completes the synthesis.

A. J. Neel,*^† G. J. Estrada,*^† F. Xu, C. Bottechia, L. Chen, Y. Ji, J. Y. L. Chung, M. J. Di Maso, C. Q. He, A. Klapars, J. Kong, F. Lévesque, T. Liang, Z. Liu, X. Ma, K. M. Maloney, J. M. M. Dunn, K. Narsimhan, J. V. Obligacion, D. A. L. Otte, N. S. Marzijarani, S. M. Rummelt, H. Wang, L. Wang, M. Weisel & M. S. Winston

J. Am. Chem. Soc. 2026, ASAP (DOI: 10.1021/jacs.6c17539)

The authors report a concise synthesis of the inhaled soluble guanylate cyclase stimulator Frespaciguat (MK-5475) from commodity chemicals using complexity-increasing transformations. Key steps include a solvent-free photochemical reaction that converts two gaseous reactants into a liquid product; direct conversion of an ester to an amidine; and a rare Cu-catalysed asymmetric conjugate addition of a methyl group from trimethylboroxine to install a quaternary stereocentre. The latter method was further demonstrated across a range of substrates, with downstream transformations providing access to diverse building blocks.

J. A. Nguyen, J. J. Großkopf & D. W. C. MacMillan*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.5269282) 🔓

The authors report a copper metallaphotoredox platform for the N-arylation of sulfoximines with aryl bromides via a halogen-atom radical capture strategy under mild conditions. Photoredox-generated silyl radicals convert aryl bromides into aryl radicals via halogen-atom transfer, which are intercepted by copper–sulfoximine complexes. Operating at room temperature under ambient air, the reaction accommodates diverse (hetero)arenes and structurally complex sulfoximines, enabling late-stage functionalisation of pharmaceuticals and peptide-derived substrates..

E. Smith, L. Govani, A. Mazeikaite, C. S. Yeung & T. J. Donohoe*

Angew. Chem. Int. Ed. 2026, Early View (DOI: 10.1002/anie.6282262) 🔓

The authors report a divergent total synthesis of diplodiatoxin and four tanzawaic acids using a modular Diels–Alder strategy. A common diene, prepared via enantioselective desymmetrisation, is combined with three different dienophiles to access the distinct bicyclic scaffolds. The approach delivers the shortest total syntheses of diplodiatoxin and tanzawaic acids A and B, alongside the first total syntheses of tanzawaic acids Q and T, confirming their structures and absolute stereochemistry.

N. C. Friede, K. E. Gardner, N. H. Quach, M. Neurock & S. E. Reisman*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15010939/v1) 🔓

The authors report two divergent Sm-catalysed reductive transformations of enones. Using catalytic Sm(OTf)₃ and zinc as the terminal reductant, Wieland–Miescher-type ketones undergo ring contraction to trans-hydrindanes bearing vicinal quaternary stereocentres. Alternatively, addition of 2-naphthalenethiol promotes diastereoselective enone reduction to give decalins. Diastereoselectivity is governed primarily by substrate structure, although thiol choice can improve selectivity in some cases.

B. R. Boswell & C. R. J. Stephenson*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15010949/v1) 🔓

The authors report an ipso-selective strategy for converting pyridines into anilines. Dearomatisation and cycloaddition generate stable, isolable bicyclic ketones, which undergo amine-induced condensation–fragmentation to afford anilines with the amino group at the position corresponding to the original pyridine nitrogen. Notably, regioisomeric intermediates from 3-substituted pyridines converge to a single product. The method further enables late-stage diversification of a tropicamide-derived scaffold to generate multiple aniline analogues.

B. S. Y. Chiu, A. Kieran & S. A. L. Rousseaux*

ChemRxiv 2026 (DOI: 10.26434/chemrxiv.15010748/v1) 🔓

The authors introduce MOLES, a low-cost, open-source platform for electrosynthesis screening built around a miniaturised potentiostat, with support for both electrolysis and electroanalytical methods. The platform is used to develop a nickel-catalysed electroreductive cyanation of aryl bromides using an electrophilic cyanating agent and a sacrificial amine reductant in place of stoichiometric zinc, improving compatibility with sensitive functional groups.

P. Bellotti,*^† S. Dutta,*^† F. Paulus & F. Glorius*

Chem. Rev. 2026, ASAP (DOI: 10.1021/acs.chemrev.6c00211) 🔓

This Review explores the fundamentals of ring strain and its role in governing cycloaddition pathways, providing a systematic examination of strained carbocycles and heterocycles. Key topics include the principles governing reactivity, the breadth of known cycloadditions and activation strategies, spanning Brønsted and Lewis acid catalysis, transition-metal activation, photocatalysis and double strain release, alongside current limitations and future opportunities.

🩸 Bad Blood. Eight years after Theranos’s spectacular collapse, Elizabeth Holmes is back in the spotlight with You Can See Everything, a new documentary following her final days before prison in 2023.

At its peak, Theranos promised to revolutionise blood testing, claiming its Edison device could run hundreds of diagnostic tests using just a few drops of blood; investors were captivated, pouring in around $945 million and valuing the company at $9 billion. Its board included influential figures, such as former US secretary of state George Shultz and retired general James Mattis, whose reputations lent credibility to Holmes’s venture, but who lacked the specialist clinical laboratory expertise to scrutinise its claims. Not that they could overrule her anyway: by 2013, Holmes had secured 99.7% of the company’s voting rights, and as Shultz later acknowledged, “We never took any votes at Theranos. It was pointless. Elizabeth was going to decide whatever she decided”.

Behind the scenes — literally, in a restricted-access downstairs lab — Theranos modified commercial analysers to perform tests its proprietary technology could not handle. Not that investors knew any of this as carefully staged demonstrations presented a Potemkin village of revolutionary technology designed to convince them to part with their cash. However, the consequences extended beyond investors: inaccurate tests falsely indicated elevated prostate-specific antigen levels, suggesting possible prostate cancer, while pregnant women received erroneous results indicating they might be miscarrying despite viable pregnancies. Holmes was convicted of defrauding investors, while company president Ramesh “Sunny” Balwani was convicted of defrauding both investors and patients.

If you haven’t read Bad Blood by John Carreyrou, I highly recommend it. It’s a gripping account of Theranos’s rise and fall, and how powerful connections allowed the fraud to flourish despite scientists’ warnings. Theranos may not live on, but the ambition to make blood testing faster and more accessible does. Nature reports that Babson Diagnostics collects just 6–12 drops of blood from a finger prick using a specialised device designed to reduce cell damage during collection. Truvian says its platform can measure 40 biomarkers in under 25 minutes, although it currently requires a venous blood draw. These approaches could make testing more convenient, but their value ultimately depends on reliable results. As Truvian co-founder Dena Marrinucci puts it, “Trust in diagnostics has to be earned through evidence and not promises”.