The reason chemists care is that the silicon–carbon bond is everywhere in modern chemistry. Molecules containing at least one Si–C bond do not exist in nature and must be made in the lab, yet they underpin small-molecule synthesis, the total synthesis of natural products, medicinal chemistry, and polymer and materials science. Silicon swapping in for carbon can tune drug scaffolds, stabilize bioactive peptides, and improve organic semiconductors and light-emitting diodes. Despite that ubiquity, deliberately installing four different substituents on a single silicon atom remains technically punishing, especially on laboratory scale, where purification by fractional distillation of tiny, similar-boiling product mixtures is a nightmare.

The standard textbook approach starts from tetrachlorosilane or tetraalkoxysilanes and relies on sequential nucleophilic substitutions. The problem is chemoselectivity. Once the first carbon group has replaced a leaving group, the remaining three are still essentially identical, and nucleophiles show little intrinsic preference among them. Unless steric bulk happens to slow the third or fourth substitution, a mixture of four different products typically results, demanding difficult separations. Earlier workarounds from the Berlin group used cyclohexa-2,5-dien-1-yl groups as masked Si–H bonds in monosilane surrogates, but preparing the surrogates and orchestrating the deprotection chemistry was elaborate. A recent photochemical method from Wu and coworkers generated silyl radicals from hydrosilanes by hydrogen atom transfer to exchange three Si–H bonds stepwise, but it required a photochemical set-up and operationally complex procedures. A complementary top-down strategy from the same Berlin laboratory used arenium-ion-catalyzed halodealkylation of tetraalkylsilanes, achieving remarkable selectivity but rejecting aryl, vinyl, and allyl substituents entirely.

The new work revisits a reaction that the literature had essentially forgotten: bromination of a trihydrosilane with elemental bromine halts at monosubstitution. Crucially, once a silicon atom carries both an Si–H and an Si–Br bond, the two behave differently toward nucleophiles. Bromide is a far better leaving group than hydride, so a carbon nucleophile displaces bromine selectively while leaving the remaining Si–H bonds untouched. That means bromohydrosilanes act as linchpins for a bottom-up synthesis in which hydrosilanes are converted, on demand, into increasingly substituted silanes, one carbon substituent at a time.

The optimization was delightfully austere. Using the model substrate methyl(phenyl)silane, the team found that exactly one equivalent of elemental bromine in n-pentane at –78 °C delivered the monobrominated product in 91% isolated yield, with only trace amounts of doubly brominated byproduct. The hydrogen bromide formed as a byproduct is swept out by a steady nitrogen flow and trapped as hydrobromic acid in a washing bottle filled with aqueous potassium hydroxide, sidestepping the salt-formation problems that made proton scavengers impractical. Mechanistic probes supported an ionic rather than radical pathway: the reaction ran identically in the dark or with a radical scavenger present, and a cyclopropane probe survived intact with the strained ring untouched. Deuterium-labeling competition experiments gave a kinetic isotope effect of essentially one, indicating that cleavage of the Si–H bond is fast and nearly barrierless even at deep-freeze temperatures.

Selectivity was the star of the show. With two equivalents of bromine, both Si–H bonds were converted, demonstrating that the first bromination is simply much faster than the second. Temperature mattered sharply: warming to 0 °C produced messy mixtures, while room temperature boiled off the solvent. Nonpolar hydrocarbons like n-pentane and n-hexane were ideal, whereas polar solvents such as dichloromethane gave lower yields and tetrahydrofuran caused complete decomposition. Among brominating reagents, elemental bromine was unmatched; the popular reagents N-bromosuccinimide and N-bromophthalimide gave incomplete or unselective reactions, and 1,3-dibromo-5,5-dimethylhydantoin converted fully but with no monoselectivity at all. The corresponding iodination chemistry was dismissed as unappealing because iodosilanes are notoriously sensitive to moisture, air, and light.

With the core reaction secured, the team demonstrated its iterative power across an impressive structural landscape. Commercial phenylsilane was brominated in 89% yield, then treated sequentially with different aryl Grignard and organolithium reagents to build up fully substituted tetraaryl silanes in yields of 68 to 93 percent. The same logic delivered silanes combining two aryl and two alkyl groups, three different alkyl groups plus one aryl group, and even all-alkyl targets with four distinct chains, reached convergently from both hexylsilane and phenethylsilane starting points. Alkynyl substituents could be installed from lithium acetylides, and even deuterium was placed at silicon in 76 percent yield using lithium aluminum deuteride, extending the method beyond carbon substituents.

The most striking feature is chemoselectivity toward sensitive functional groups already attached to silicon. Vinyl-, allyl-, and alkynyl-substituted hydrosilanes all underwent clean monobromination at the Si–H bond without any addition of bromine to their carbon–carbon multiple bonds, a feat the authors attribute to the –78 °C temperature favoring the kinetic product. When the bromine dose was doubled, addition to the π-system did occur, confirming that Si–H bromination genuinely outcompetes the competing reaction. A thiophene ring attached to silicon likewise survived the protocol untouched, and methoxy-substituted hydrosilanes could be elaborated into quaternary silanes bearing two different heteroatom substituents, including tert-butoxy, amine, and thiol groups. In every case, the bromination–substitution sequence avoided attack on the very functionalities that conventional chlorosilane chemistry would destroy.

What makes this report resonate beyond the silicon specialist community is its sheer accessibility. No photocatalyst, no transition metal, no cryogenic expertise beyond a dry ice bath, no bespoke surrogate molecules. The experimental set-up is a three-neck flask with a nitrogen inlet, a dropping funnel, and a pair of washing bottles, with the only stated caution being to add bromine slowly at low temperature to avoid abrupt hydrogen bromide evolution. The resulting bromosilanes are colorless liquids that store under inert atmosphere at 4 °C or below. For a field where the final products of a four-substitution sequence were often unresolvable soups, a programmable, high-yielding, and scalable recipe amounts to a genuine change in what synthetic planners can attempt.

The implications stretch from drug discovery, where silicon substitution is increasingly used to tune potency and metabolic stability, to materials science, where defined heteroleptic silanes serve as building blocks for optoelectronic polymers and siloxane architectures. The Berlin authors summarize the success of their strategy in three pillars: highly selective monobromination of di- and trihydrosilanes, selective displacement of bromide over hydride at silicon, and excellent compatibility with sensitive unsaturated and heteroatom-containing groups. Sometimes the most viral idea in chemistry is not a flashy new catalyst but a rediscovered reaction, executed with discipline, that makes the impossible routine. In teaching an overlooked bromine-for-hydrogen swap to obey, this team has handed synthetic chemists a modular dial for one of the periodic table’s most versatile atoms.

Subject of Research: Stepwise synthesis of heteroleptic organosilanes via selective monobromination of hydrosilanes

Article Title: Stepwise and chemoselective installation of carbon substituents at silicon atoms via monobromination of hydrosilanes

Article References: Singh, S., Randt, T., Klare, H. F. T., & Oestreich, M. (2026). Stepwise and chemoselective installation of carbon substituents at silicon atoms via monobromination of hydrosilanes. Nature Synthesis. https://doi.org/10.1038/s44160-026-01178-2

Image Credits: AI Generated

DOI: 10.1038/s44160-026-01178-2

Keywords: organosilicon chemistry, hydrosilanes, monobromination, heteroleptic silanes, Si–C bonds, synthetic methodology, chemoselectivity, nucleophilic substitution, functional-group tolerance, Nature Synthesis, silicon building blocks, elemental bromine

Allylic amines are everywhere in biologically active chemistry. They appear as substructures in natural products, in pharmaceutical candidates, and in the alkene isosteres used to mimic peptide bonds in drug design. Their appeal as building blocks goes beyond mere prevalence: because an allylic amine carries an alkene, an amine and a stereocentre in close proximity, each of these reactive sites can be manipulated independently, a property chemists describe as orthogonal reactivity. That versatility makes them ideal launch pads for constructing value-added targets, from aza-heterocycles to modified alkaloids. Yet most existing routes to their chiral versions rely on pre-activated substrates such as allylic acetates, on stoichiometric chiral auxiliaries, or on multi-step sequences that erode efficiency.

The conceptual heart of the new method is homologation — the controlled lengthening of a molecular skeleton. Homologation strategies have enjoyed a renaissance in recent years, with one-carbon extensions of carboxylic acids, alkenes and organoboron compounds all demonstrating how growing a carbon chain catalytically can shortcut traditional synthesis. The Shu group applies this logic to enamines, nitrogen-substituted alkenes that are cheap, electron-rich and easily prepared from carbonyl compounds. By coupling an enamine with an alkyne under nickel catalysis, the reaction effectively inserts the alkyne-derived fragment onto the enamine framework, converting it into an allylic amine that is one hydrocarbon unit longer and, crucially, chiral.

Technically, the transformation is an enantioselective C(sp2)–C(sp3) cross-coupling, a class of reaction that has become one of the most competitive arenas in modern catalysis. Nickel is the metal of choice for several reasons: it is earth-abundant compared with palladium, it readily shuttles between oxidation states, and it tolerates the kind of unactivated alkyl intermediates that would decompose on more precious metals. In the reported system, a chiral ligand environment around nickel governs both the regiochemistry — which carbon of the alkyne receives which partner — and the enantioselectivity, delivering products in good yields with excellent enantiomeric excess across a broad substrate scope.

Perhaps the most striking feature is the chemoselectivity that makes the reaction possible at all. Mechanistic investigations by the team revealed that the catalytic cycle hinges on a selective hydrometallation step in which nickel hydride adds preferentially to the electron-rich alkene of the enamine rather than to the more electrophilic linear alkyne present in the same flask. That preference runs counter to what simple electronic intuition might predict, since electrophilic alkynes typically react faster with metal hydrides. By favouring the less obvious partner, the catalyst generates an alkyl-nickel species that then engages the alkyne in the bond-forming event, setting up the stereochemistry-defining step of the cycle.

The scope of the reaction, documented across the paper’s substrate tables and crystallographically confirmed structures, spans a wide range of alkynes and enamines. Six crystal structures deposited with the Cambridge Crystallographic Data Centre underpin the structural assignments, giving the community unambiguous three-dimensional confirmation of the products’ configurations. The breadth matters practically: medicinal chemists rarely work with a single substrate class, and a method that accommodates varied substitution patterns on both coupling partners is far more likely to be adopted in late-stage or discovery settings than one restricted to narrow examples.

The synthetic utility is demonstrated most convincingly in the applications section, where the authors show that the reaction provides a convenient route to a range of bioactive molecules and key intermediates. Among the targets accessible through the chemistry are motifs related to monoamine oxidase inhibitors and CCR3 antagonist scaffolds, compounds whose chiral allylic amine cores have traditionally demanded lengthy asymmetric sequences. Because the products retain multiple reactive handles — the alkene, the amine and any additional functionality inherited from the alkyne — they can be elaborated further, meaning the reaction functions not just as an endpoint but as a strategic gateway within a longer synthesis.

The work also fits into a broader pattern in the Shu group’s research programme, which has focused on nickel-catalysed asymmetric cross-hydrodimerization and hydroalkylation reactions of unsaturated partners. Earlier contributions from the same laboratory include enantioselective alkyl–alkyl couplings of alkenes and cobalt-catalysed cross-hydrodimerizations of dienes with alkynes. The new enamine homologation extends this reactivity-mode thinking to nitrogen-containing substrates, showing how the same mechanistic family — hydrometallation followed by controlled C–C bond formation — can be redirected toward different product classes by changing the coupling partners and ligand design.

For the pharmaceutical industry, the significance is twofold. First, the method converts commodity starting materials into high-value chiral intermediates in a single step, which translates directly into fewer operations, less waste and lower cost in process chemistry. Second, because the products are enantioenriched aliphatic allylic amines rather than aryl-substituted analogues, the chemistry reaches a subclass that asymmetric hydrogenation and classical imine alkenylation methods have served poorly. Homologation itself is increasingly recognised in medicinal chemistry as a powerful strategy for exploring the property space around a lead compound, and a catalytic, enantioselective homologation of amines gives drug hunters a new dial to turn when optimising potency, selectivity and metabolic stability.

The study, supported by the National Natural Science Foundation of China and regional funding bodies in Guangdong and Sichuan, was peer reviewed at Nature Synthesis with crystallographic and mechanistic evidence available in the supplementary materials. As nickel catalysis continues to displace precious-metal chemistry across the synthesis landscape, this enamine-to-allylic-amine homologation stands out as a template for how careful mechanistic insight — here, the counterintuitive selectivity of hydrometallation — can unlock transformations that were previously out of reach, and it is likely to inspire a wave of follow-up work aimed at extending homologation logic to other functional groups and feedstock combinations.

Subject of Research: Nickel-catalysed regio- and enantioselective homologation of enamines with alkynes to synthesize chiral allylic amines

Article Title: Synthesis of chiral allylic amines through regio- and enantioselective homologation of enamines using Ni catalysis

Article References: Du, Y.-M., You, L.-X., Li, Y.-L., Yu, Q., & Shu, W. (2026). Synthesis of chiral allylic amines through regio- and enantioselective homologation of enamines using Ni catalysis. Nature Synthesis. https://doi.org/10.1038/s44160-026-01172-8

Image Credits: AI Generated

DOI: 10.1038/s44160-026-01172-8

Keywords: nickel catalysis, chiral allylic amines, enamines, alkynes, homologation, asymmetric catalysis, cross-coupling, hydrometallation, reaction mechanism, drug discovery, synthetic methodology, Nature Synthesis

The appeal of 3,3-diaryloxetanes stems from their role as bioisosteres of diaryl ketones. Bioisosteric replacement is a cornerstone strategy in drug design: chemists swap one functional group for another that mimics its key electronic and spatial characteristics while improving properties such as solubility, stability or potency. Diaryl ketones, the motif in which two aromatic rings flank a central carbonyl group, appear in numerous marketed pharmaceuticals, including the anti-inflammatory drug ketoprofen, the lipid-lowering agent fenofibrate, the antidiabetic compound adiporon and the antiarrhythmic amiodarone. The polarized carbon–oxygen double bond of the ketone generates a substantial dipole moment, typically around 2.7 to 3.0 Debye, which shapes how the molecule interacts with biological targets through electrostatic contacts and molecular recognition.

Oxetanes reproduce much of this electronic character through an entirely different structural principle. The ring oxygen withdraws electron density through sigma-bond polarization, and the two polarized carbon–oxygen bonds of the strained ring collectively generate a dipole of roughly 1.93 Debye, comparable in effect to the carbonyl dipole. Replacing a flat, planar carbonyl with a tetrahedral oxetane therefore preserves overall polarity while introducing a three-dimensional centre into the molecule, a change that can dramatically alter binding geometry and metabolic fate. Crucially, however, oxetanes and ketones differ fundamentally in reactivity. The carbonyl carbon of a ketone is intrinsically electrophilic because of its low-lying pi-star orbital, whereas oxetanes lack a pi system altogether, and their polarity is distributed across the ring. No carbon on an oxetane behaves like a carbonyl carbon, which means the two motifs can be electronically similar yet chemically orthogonal, an ideal combination for drug design.

Despite this conceptual elegance, synthetic access to 3,3-diaryloxetanes has lagged far behind. The dominant approach, pioneered by James Bull and co-workers, relies on Lewis acid-promoted Friedel–Crafts reactions that proceed through oxetanyl cation intermediates. These reactive intermediates are inherently unstable, and the strongly acidic conditions required restrict the method largely to electron-rich arenes, with competing ring-opening and rearrangement pathways eroding yields and selectivity. Recent iron-catalysed variants have broadened the substrate scope somewhat, but the fundamental limitations of cation chemistry remain. An alternative strategy developed by Phil Baran uses decarboxylative coupling of oxetane-3-carboxylic acid derivatives, generating tertiary benzylic radicals that can engage in cross-coupling. However, these radicals are prone to oxidation to carbocations or reduction to carbanions through radical-polar crossover, and the method demands multistep precursor synthesis and costly starting materials, limiting its practicality and scalability.

The Ritter group’s solution reimagines the problem through the lens of transition-metal catalysis. The chemists hypothesized that converting 3-aryl oxetan-3-ols into electrophiles suitable for nickel-catalysed cross-coupling would provide a modular route, provided they could overcome a formidable obstacle: oxidative addition at the sterically congested carbon–oxygen bond of a fully substituted oxetanyl centre. Such bonds combine steric hindrance with limited intrinsic polarization, disfavouring the oxidative addition step that initiates most cross-coupling cycles. Their answer was to install a tetrafluoropyridyl ether as the leaving group. This electron-deficient aromatic unit polarizes the carbon–oxygen bond and stabilizes the departing tetrafluoropyridone through pi delocalization, striking an optimal balance between reactivity and stability. Unlike strongly electron-withdrawing leaving groups such as triflates, which promote elimination and solvolysis when tertiary benzylic cations form, the tetrafluoropyridyl unit enables controlled activation while its low nucleophilicity and weak basicity suppress ring-opening side reactions.

The practical execution is strikingly simple. In the first step, an aryl bromide is lithiated with n-butyllithium and added to 3-oxetanone, and the resulting alkoxide is trapped in the same pot with pentafluoropyridine to form the oxetanyl tetrafluoropyridyl ether. This one-pot sequence delivered a model substrate in 89 percent yield on a 6.2-gram scale, and the addition of sodium hydride before the trapping step boosted yields by roughly 46 percent. The resulting ethers are bench-stable reagents that can be stored at room temperature for at least six months without detectable decomposition, a critical attribute for a method intended for widespread adoption. Grignard reagents can substitute for the aryllithiums, though the ether formation then works better as a separate step.

The second step is a nickel-catalysed Suzuki-type coupling with arylboronic esters. Using 10 mole percent Ni(cod)2, potassium phosphate as base and isobutanol as an additive in tetrahydrofuran at 30 degrees Celsius, the model coupling afforded the 3,3-diaryloxetane product in 99 percent yield. Control experiments confirmed that every component matters: removing the nickel catalyst or the base eliminated product formation entirely, while omitting the alcohol additive dropped the yield to 73 percent, likely because the alcohol promotes transmetalation of the boronic ester. Notably, palladium catalysts and common nitrogen and phosphine ligands such as dtbbpy and dppf suppressed the reaction, suggesting that strongly coordinating ligands inhibit formation of the reactive nickel species, whereas pi-accepting olefin additives such as 4-methoxystilbene maintained efficiency and may stabilize the catalytically active complex.

The substrate scope demonstrates the modularity that has been missing from this field. Both electron-rich and electron-deficient aryl bromides were converted to the ether precursors in 80 to 95 percent yields on 5-millimole scale, and heteroaromatic motifs including indole, benzothiophene, benzofuran, furan and quinoline were all incorporated. On the coupling side, electron-poor arylboronic esters, heteroaryl boronates and even alkenyl boronic esters performed smoothly, a striking contrast to Friedel–Crafts chemistry, where such substrates are typically unreactive because reactivity there depends on arene nucleophilicity rather than metal-catalysed processes. A methyl ester-bearing product was obtained in 95 percent yield on gram scale. Late-stage diversification succeeded on complex molecules including fenbufen, estrone, tocopherol, flurbiprofen and pyriproxyfen, and the method extended to 3,3-diaryl azetidines, although cyclobutane analogues remain out of reach because their tetrafluoropyridyl ethers are too unstable to isolate.

The synthetic payoff is best illustrated through drug analogues. The team prepared oxetane versions of scaffolds related to ketoprofen, oxybenzone, fenofibrate and a tyrosine kinase inhibitor, and assembled an oxetane analogue of adiporon, a drug candidate for type 2 diabetes, in 65 percent yield after deprotection and amide formation. Most dramatically, a KIT inhibitor intermediate was reached in 20 percent overall yield over two steps from 3-oxetanone, whereas a previous route required four steps and delivered only 0.1 percent overall yield. A second intermediate was obtained in 58 percent yield over two steps compared with 22 percent across four steps previously, and it can be advanced to a complement C1s inhibitor by established procedures.

Mechanistic studies support a conventional but hard-won catalytic cycle. Stoichiometric and catalytic nickel both delivered high yields, and experiments with the one-electron oxidant ferrocenium showed that nickel(I) cannot sustain turnover, implicating nickel(0) as the active species. The radical scavenger BHT had little effect, while TEMPO completely inhibited the reaction with quantitative recovery of starting material, consistent with a polar pathway free of radicals, though TEMPO is also known to oxidize low-valent nickel directly. A Hammett analysis gave a shallow negative reaction constant of minus 0.49, indicating only weak dependence on aryl electronics. Together the data point to a Ni(0)/Ni(II) manifold of oxidative addition, transmetalation and reductive elimination, distinct from the Ni(I)/Ni(III) radical pathways common in modern cross-coupling. The work establishes tetrafluoropyridone as a leaving group worth exploring more broadly and hands medicinal chemists a programmable, two-step entry to benzophenone bioisosteres that were previously among the most difficult scaffolds to access.

Subject of Research: Modular nickel-catalysed synthesis of 3,3-diaryloxetanes as ketone bioisosteres from 3-oxetanone

Article Title: Modular synthesis of 3,3-diaryloxetanes

Article References: Sun, Q., Liu, J., & Ritter, T. (2026). Modular synthesis of 3,3-diaryloxetanes. Nature Synthesis. https://doi.org/10.1038/s44160-026-01183-5

Image Credits: AI Generated

DOI: 10.1038/s44160-026-01183-5

Keywords: oxetanes, bioisosteres, nickel catalysis, cross-coupling, 3-oxetanone, drug discovery, medicinal chemistry, tetrafluoropyridyl ether, oxidative addition, synthetic methodology, diaryl ketones, heterocycles

Multicomponent reactions are prized in organic synthesis because they stitch together three or more simple molecules in a single operation, rapidly building molecular complexity and diversity while minimizing purification steps. Yet this efficiency comes with a catch. When several nucleophiles—electron-rich species that donate electron pairs to form new bonds—are present in the same flask, they tend to compete for the same electrophilic partner, producing chaotic mixtures of products. Chemists have long coped with this by pre-functionalizing substrates, installing protecting groups or activating handles that exaggerate the reactivity differences between partners. Such workarounds add steps, generate waste and undermine the atom economy that makes multicomponent chemistry attractive in the first place.

The new study takes a different tack. Rather than modifying the nucleophiles themselves, the researchers exploited the dual personality of a palladium–propargyl complex, a reactive intermediate generated when a palladium catalyst engages a propargylic carbonate—a common and easily prepared class of propargyl electrophiles. When palladium inserts into the carbon–oxygen bond of the carbonate with loss of carbon dioxide, it forms what chemists call an η3-propargyl–palladium species. Crucially, this intermediate can be represented as two resonance forms: a propargyl form and an allenyl form. The team recognized that this tandem reactivity could serve as a built-in sorting mechanism, offering two distinct electrophilic targets within the same metal complex.

The sorting logic works as follows. Stronger nucleophiles in the reaction mixture undergo outer-sphere addition to the propargyl–palladium intermediate, attacking the organic ligand directly from outside the coordination sphere of the metal. Weaker nucleophiles, by contrast, cannot compete on reactivity alone. Instead, they are guided by their superior coordinating affinity—their tendency to bind directly to the palladium center. Once coordinated, these weaker partners attack the resulting allyl–palladium species through an inner-sphere mechanism, in which the bond-forming event occurs from within the metal complex. The two pathways are orthogonal: each class of nucleophile is routed to a different intermediate and a different position in the product, purely on the basis of its intrinsic physical properties.

This elegant division of labor allows the precise recognition and ordered incorporation of diverse pairs of native N–H and O–H nucleophiles—amines and alcohols bearing no protecting groups or artificial activation. The upshot is a modular platform for constructing chiral 1,2-amino alcohols and 1,2-diols with what the authors describe as exceptional regio-, chemo-, Z- and enantiocontrol. In practical terms, the reaction decides correctly which nitrogen or oxygen attaches where along the carbon chain, whether the alkene geometry is the Z isomer, and which enantiomer of the product predominates—all in a single catalytic operation starting from fundamental feedstock chemicals.

The significance of that selectivity profile is hard to overstate. Vicinal amino alcohols—molecules bearing an amine and an alcohol on adjacent carbons—are among the most consequential chiral building blocks in chemistry. The cis-1-amino-2-indanol core, for example, features prominently in drug design and asymmetric processes, as documented in a classic Chemical Reviews survey. Amino alcohol motifs appear in HIV protease inhibitors, in the plant growth regulator uniconazole, in antitussive Stemona alkaloids such as stemoninine, and in daryamide natural products isolated from marine Streptomyces bacteria. Beyond their presence in bioactive molecules, amino alcohols and their heterocyclic derivatives serve as chiral auxiliaries and as nitrogen-containing ligands for asymmetric catalysis, including the widely used pyridine–oxazoline family.

Existing routes to enantioenriched amino alcohols each carry limitations. Asymmetric hydrogenation of prochiral amino ketones, pioneered for pharmaceutical manufacturing, requires specialized equipment and carefully matched catalysts. The Sharpless asymmetric aminohydroxylation of olefins, introduced in 1996, delivers vicinal amino alcohols directly but is constrained in scope by its osmium-based chemistry. Subsequent decades brought copper-catalyzed radical oxyfunctionalization of alkenes, palladium-catalyzed aminoacetoxylation, iridium nitrenoid chemistry, organoiodine-catalyzed oxyamination and rhodium-catalyzed diene functionalization—each expanding the toolbox, yet typically demanding pre-oxidized or specially activated substrates, or delivering only one of the two heteroatoms from a reagent that must be synthesized in advance. The new palladium strategy sidesteps much of this preparative burden by drawing both heteroatom sources directly from native, unprotected nucleophiles.

The choice of propargylic carbonates as the linchpin substrate reflects a decade of methodological development in palladium-catalyzed propargylic substitution. Because the η3-propargyl–palladium intermediate can react at different positions and through different mechanistic manifolds, controlling regio-, chemo- and enantioselectivity simultaneously has been a recognized challenge. Earlier work from the Chen group established regiodivergent syntheses of 1,3-dienyl and allyl esters from propargyl esters, and related studies across the field have harnessed these intermediates for allenylations, annulations and cascade dearomatizations. The present work adds a genuinely new dimension: using the intermediate’s dual electrophilicity not merely to diversify products, but to impose an ordering on competing nucleophiles.

Mechanistic evidence underpins the proposal. Time-course and kinetic studies traced the multicomponent alkenylation process and the roles of individual reaction components, while density functional theory calculations, carried out by Tingrui Liu with Bingnan Du, rationalized the orderly incorporation of the nucleophiles and mapped the energetic landscape of the competing pathways. Extended optimization studies probed how nucleophile basicity, expressed as pKa in water, influences the outcome, and control experiments without the bisphosphine ligand DPPB underscored its necessity. Crystallographic support came from X-ray structures deposited at the Cambridge Crystallographic Data Centre under deposition numbers CCDC 2212247 and 2418501, anchoring the stereochemical assignments that the enantiocontrol claims rest upon.

The broader conceptual payoff may prove as important as any individual product. The study demonstrates that subtle reactivity differences—differences far too small to exploit through conventional chemoselectivity—can be systematically harnessed when a catalyst offers multiple, mechanistically distinct reactive channels. In this sense the palladium complex functions less like a conventional reagent and more like a sorting machine, reading the nucleophilicity and coordinating affinity of each partner and dispatching it accordingly. The approach echoes recent advances in amine sorting for unsymmetrical diamines and ureas, and suggests a general design principle for programmable synthesis: rather than forcing all partners down a single reaction pathway, engineers of future multicomponent reactions may deliberately build catalysts with parallel, orthogonal channels tuned to the intrinsic properties of the molecules they wish to combine. For a field striving to make complex, enantiopure molecules directly from simple feedstocks with minimal waste, that is a compelling blueprint.

Subject of Research: Palladium-catalysed orthogonal multicomponent synthesis of enantiopure 1,2-amino alcohols

Article Title: Orthogonal nucleophile-ordered assembly for modular access to enantiopure 1,2-amino alcohols

Article References: Dai, M., Liu, T., Zhang, M., Zhang, L., Zhang, M., Song, L., Du, B., & Chen, L.-A. (2026). Orthogonal nucleophile-ordered assembly for modular access to enantiopure 1,2-amino alcohols. Nature Chemistry. https://doi.org/10.1038/s41557-026-02263-x

Image Credits: AI Generated

DOI: 10.1038/s41557-026-02263-x

Keywords: palladium catalysis, multicomponent reactions, 1,2-amino alcohols, asymmetric catalysis, propargylic carbonates, chemoselectivity, enantioselectivity, nucleophile sorting, propargyl-palladium complexes, synthetic methodology, chiral ligands, organic synthesis

Carbon-carbon bond formation is the backbone of organic synthesis, and the reactions that accomplish it define what molecules are practically accessible. Bonds between two sp3-hybridised carbons, the tetrahedral carbons that give molecules their three-dimensional shape, are particularly valuable. Saturated, three-dimensional frameworks are strongly associated with success in drug development, a trend famously described as escaping flatland, because flat, aromatic-rich molecules often suffer from poor solubility and off-target effects. Yet while chemists have become adept at stitching together flat sp2 carbons through classic cross-coupling chemistry, the alkyl-alkyl variant remains far more difficult, because the reactive intermediates involved are short-lived and prone to unproductive side reactions.

One powerful way to make sp3-sp3 bonds is radical chemistry. Radicals, species bearing an unpaired electron, are notoriously reactive, which makes them both useful and dangerous in a synthesis flask. When two radicals meet, they can combine to form a new carbon-carbon bond, a process known as radical-radical cross-coupling. The catch is controlling the encounter. Most successful strategies to date rely on pairing a persistent radical, one that survives long enough to accumulate in solution, with a transient radical, one that lives for only a fleeting moment. The persistent radical effect then steers the chemistry toward selective cross-coupling rather than a chaotic mixture of products. Directly coupling two transient radicals, both generated from separate precursors, has remained a formidable challenge.

There is one venerable exception: Kolbe electrolysis, first described by Hermann Kolbe in 1849. In this electrochemical process, carboxylic acids are oxidised at an anode, losing an electron and releasing carbon dioxide to generate carbon-centred radicals that then dimerise. Kolbe electrolysis is one of the few methods capable of directly coupling two transient radicals, but it works best when both radicals come from the same or very similar carboxylic acids. Getting radicals from two chemically distinct precursors, say a carboxylic acid on one side and a boronic acid on the other, to meet and combine selectively has largely been out of reach, because the two precursors oxidise at different potentials and their radicals tend to react with themselves rather than with each other.

The Northwestern team’s solution rests on two intertwined ideas. The first is redox-matched alternating-polarity electrolysis. Instead of applying a constant current in one direction, the researchers alternate the polarity of the electrodes, so that each half-cycle generates one type of radical under conditions matched to its own oxidation chemistry. This waveform control allows carboxylic acids to be oxidised to alkyl radicals during one polarity phase, while organoboron reagents are activated during the complementary phase, giving both radical pools a chance to coexist and combine. Alternating current electrolysis has been gaining momentum in organic electrosynthesis precisely because it lets chemists run incompatible oxidative and reductive events in the same vessel, and the team’s earlier mechanistic work on alternating-polarity electrolysis for carbon-centred radical generation laid the groundwork for the present advance.

The second idea is controlled activation of redox-active species through fluoride. Organoboron reagents are not normally easy to oxidise directly, but the researchers used controlled fluoride activation to tune the redox behaviour of the boronic acids, making them competent radical precursors under the electrolysis conditions. Cyclic voltammetry studies, an electrochemical technique that maps out at which potentials molecules gain or lose electrons, helped the team identify the redox-matched window in which both precursors could be activated without one simply overwhelming the other. By carefully choreographing electrode polarity and chemical activation, the method achieves what conventional constant-current electrolysis cannot: a productive meeting of two transient radicals born from entirely different functional groups.

The scope of the transformation is what makes the result more than an electrochemical curiosity. The researchers demonstrated the cross-coupling of alkyl carboxylic acids with alkyl boronic acids to form sp3-sp3 carbon-carbon bonds, exactly the connectivity that is prized in drug-like scaffolds but difficult to access. They also showed that the platform extends to homocoupling reactions, in which two identical fragments are joined, and to a net carboxylic acid-alkene cross-coupling. In the latter variant, an alkene is first converted in situ into an alkyl boronic acid through hydroboration, the addition of a boron-hydrogen bond across the double bond, and the resulting boronic acid then enters the electrolytic coupling. This effectively lets chemists use cheap, widely available alkenes as radical precursors without isolating the intermediate.

Perhaps most striking is the way the new chemistry dovetails with established catalytic reactions. The team showcased tandem processes in which the electrochemical radical coupling is combined with Suzuki coupling, the palladium-catalysed workhorse reaction that joins boronic acids with aryl halides, and with Buchwald-Hartwig amination, which forms carbon-nitrogen bonds. This means a single molecular sequence can build a carbon-carbon bond electrochemically and then diversify the product through trusted catalytic steps, multiplying the value of each starting material. For medicinal chemists, who routinely need to prepare families of closely related analogues to optimise a drug candidate, such downstream diversification from a common carboxylic acid-boronic acid coupling product is exactly the kind of flexibility that accelerates discovery.

The significance of the work lies in the feedstocks as much as in the chemistry. Carboxylic acids and organoborons are among the most plentiful and well-behaved functional groups in the synthetic repertoire, stable enough to store and handle, and available in enormous structural variety. Electrochemistry itself has undergone a renaissance in the past two decades, because electricity can serve as a clean, tunable oxidant or reductant, replacing stoichiometric chemical oxidants and offering precise control over reaction outcomes through potential and current. By merging waveform-controlled electrolysis with rational redox matching, the Northwestern group has pushed that renaissance into territory that classical methods, including more than a century and a half of Kolbe chemistry, could not reach.

There remain practical considerations before such methods become routine. Alternating-polarity electrolysis requires equipment and optimisation that many synthetic laboratories are still adopting, and the interplay of electrode material, supporting electrolyte, solvent and waveform parameters demands careful tuning for each new substrate combination. The mechanistic picture, probed through cyclic voltammetry and experimental studies of radical generation, will continue to be refined as the community explores the boundaries of the approach. Nevertheless, the demonstration that two transient radicals from distinct, abundant precursors can be generated in the same pot and persuaded to couple selectively marks a genuine expansion of what electroorganic synthesis can do. For a field whose ultimate goal is to make any desired molecule efficiently, sustainably and in three dimensions, the ability to weld carboxylic acids and organoborons together with nothing more than electrons is a milestone worth watching.

Subject of Research: Electrochemical radical-radical cross-coupling of alkyl carboxylic acids and organoboronic acids

Article Title: The radical-radical cross-coupling of alkyl carboxylic acids and organoborons

Article References: Zhong, J., Boudjelel, M., Evans, J. M., Vanswearingen, I., & Malapit, C. A. (2026). The radical-radical cross-coupling of alkyl carboxylic acids and organoborons. Nature Chemistry. https://doi.org/10.1038/s41557-026-02237-z

Image Credits: AI Generated

DOI: 10.1038/s41557-026-02237-z

Keywords: electrochemistry, radical cross-coupling, carboxylic acids, organoborons, Kolbe electrolysis, C(sp3)-C(sp3) bonds, organic synthesis, alternating polarity electrolysis, Nature Chemistry, synthetic methodology, persistent radical effect, medicinal chemistry

The significance of the target scaffolds is hard to overstate in medicinal chemistry terms. The parent 2-azabicyclo[3.1.0]hexane motif, in which a cyclopropane ring is fused to a pyrrole or indole core, is isosteric with quinoline, meaning it occupies a similar three-dimensional shape while offering different electronic properties. Fusing the rigid cyclopropane onto the nitrogen heterocycle reduces the lipophilicity of the parent pyrroline, alters the electronic environment around the nitrogen atom, and introduces new exit vectors that drug designers can exploit to tune biological activity. Star molecules built on this framework include SUVN-911, a potent α4β2 nicotinic receptor ligand with a strong safety profile at high doses, an inhibitor of NF-κB-inducing kinase, and saxagliptin, the widely used oral dipeptidyl peptidase IV inhibitor for type 2 diabetes.

Yet the two scaffolds targeted in the new study, which carry an additional degree of unsaturation or a third fused ring, have remained chemical backwaters. According to the authors, the reason is simple: practical synthetic routes are scarce, and those that exist tend to involve long sequences, low overall efficiency, and little structural diversity. The team’s own earlier work hints at why closing this gap matters. When they previously incorporated an extra nitrogen into the 2-azabicyclo[3.1.0]hexane framework, the resulting diazabicyclo[3.1.0]hexanes showed promising anti-proliferative activity, suggesting that small structural edits to these rigid frameworks can translate into meaningful pharmacological effects.

Retrosynthetically, chemists have generally attacked these targets in one of two ways. The first strategy constructs the cyclopropane ring onto an existing pyrrole or pyrrolidine core; the second forges both rings simultaneously in a single operation, exemplified by a copper-catalyzed intramolecular reductive isocyanide-alkene (1+2) cycloaddition that gives direct access to 2-azabicyclo[3.1.0]hexanes. While the tandem approach is elegant, the authors note that limitations in preparing the substrates restrict its usefulness for building compound libraries, a critical consideration for medicinal chemistry screening campaigns.

Cyclopropanation of indoles with metal carbenoids has long looked like an attractive route to the benzo-fused analogues, but it comes with a stubborn problem. When 2,3-non-substituted indoles are treated with diazo compounds under various transition-metal catalysts, the desired cyclopropanation competes with formal C(sp2)-H bond alkylation, eroding selectivity and yield. In 2019, Sen and coworkers reported the first selective cyclopropanation of N-acylindoles using aryl diazo esters as donor-acceptor carbenes with a manganese catalyst, but only moderate diastereoselectivities were achieved, with no assignment of the major isomer’s relative configuration. A year later, the Lautens group swapped diazo compounds for cyclopropenes in the cyclopropanation of indoles, benzofurans, and related aromatics, while Jiang and Loh showed that the N-protecting group critically controls the E/Z geometry of the alkene in the product. Even so, selectivity remained unsolved, and pyrroles, which are electronically distinct from their benzofused indole cousins, had never been explored in this chemistry.

The Zhao group’s long-standing expertise in cyclopropene chemistry provided the opening. Cyclopropenes are high-energy, strained three-membered alkenes that transition metals can ring-open to generate alkenyl carbenoids, reactive intermediates capable of cyclopropanating a second π-system. Most catalytic cyclopropanations with cyclopropene precursors had been limited to simple alkenes, with few examples involving electron-rich arenes. Pyrroles are among the most electron-rich aromatic rings known, which makes them reactive but also difficult to control. The team reasoned that dialing back the pyrrole’s reactivity through electronic fine-tuning of the nitrogen substituent could be the key to clean, selective cyclopropanation.

That reasoning proved correct, but only after careful optimization. Because bis-cyclopropanation at both ends of the pyrrole ring would create spiro products with uncontrollable stereochemistry, the chemists started with pyrroles in which one side is blocked, using a cyclohexanone-fused pyrrole derivative as the test substrate. After screening N-protecting groups, they found that simple N-methyl and N-benzyl pyrroles gave no product at all. Introducing electron-withdrawing acyl groups changed everything: a tert-butoxycarbonyl group gave a 45 percent yield, while a benzoyl group boosted the yield to 84 percent. The best result, 91 percent, came from a 3,5-bis(trifluoromethyl)benzoyl group, paired with the dirhodium tetracetate catalyst Rh2(OAc)4 in benzene solvent. Solvent screening showed the reaction is remarkably picky, with toluene, dichloromethane, chlorobenzene, THF, and acetonitrile all giving dramatically lower yields or trace product. Strikingly, across every condition examined, the diastereomeric ratio and E/Z selectivity exceeded 25 to 1.

With the optimized conditions in hand, the team mapped the substrate scope. On the cyclopropene partner, strongly electron-withdrawing trifluoromethyl and strongly electron-donating methoxy groups on the aryl ring were both tolerated in excellent yields, as were para-alkyl, chloro, bromo, and naphthyl substituents. The reaction proved sensitive to substitution position: meta-substituted aryl groups gave comparable yields to their para counterparts, but ortho-substituted analogues suffered significantly reduced yields and lower E/Z ratios. Cyclopropenes bearing alkyl groups other than methyl at the carbenoid carbon also performed well, delivering products in 72 to 96 percent yields, and 3,3-dialkyl substitution was tolerated, although two alkyl groups of similar steric bulk dropped the E/Z ratio to an even 52:48. The team also revisited indoles, finding that a 4-methoxybenzoyl protecting group was optimal there, with the reaction reaching 63 percent conversion in 24 hours and the product isolated in 85 percent yield based on recovered starting material but with only a 40:60 E/Z ratio, a comparison that highlights the distinct electronic demands of indole versus pyrrole in this chemistry. Finally, unblocked pyrroles underwent double cyclopropanation to give the biscyclopropanated polycyclic 5-azatricyclo[4.1.0.0^(2,4)]heptane products in moderate to good yields and high diastereoselectivities.

The proposed mechanism explains both the efficiency and the stereochemical outcome. Rh2(OAc)4 first ring-opens the cyclopropene to form a vinyl rhodium carbene complex. The electron-rich pyrrole then attacks this electrophilic carbenoid, generating a zwitterionic rhodium-containing intermediate. Because controlling stereochemistry at the carbene-forming step is inherently difficult, the authors propose that the high E/Z selectivity arises instead from an equilibrium between two zwitterionic complexes, followed by rhodium migration and rotation about a carbon-carbon bond that funnels the reaction toward the thermodynamically favored E-isomer. The ortho-substitution effect fits this picture: steric clash, described as A^(1,3)-strain, in the carbenoid and the subsequent adduct hinders cyclization and can trigger rotation of the allylic rhodium moiety before ring closure, increasing the proportion of Z-product. An instructive control experiment used ethyl diazoacetate, a conventional carbene precursor that would generate a similar alkenyl carbenoid, and produced no product at all, leaving open the question of whether the alkenyl moiety itself drives the high diastereoselectivity. Regardless, the authors point out that using cyclopropene installs an extra alkene handle in the product that can be elaborated further, adding synthetic value beyond the cyclopropanation itself.

The upshot is a protocol characterized by simple operation, mild conditions, low catalyst loading, and high yields and stereoselectivities, with good tolerance for variation on both reaction partners. That combination is exactly what medicinal chemists need to rapidly assemble libraries of these rigid, nitrogen-rich frameworks for biological screening, particularly given the track record of related scaffolds in approved drugs and the team’s own evidence that adding heteroatoms to these bicyclic systems can unlock anti-proliferative activity. The authors report that efforts to expand the reaction’s applications are already underway, and if those efforts succeed, the once-neglected 2-azabicyclo[3.1.0]hex-3-ene and 5-azatricyclo[4.1.0.0^(2,4)]heptane frameworks may soon join the ranks of routinely deployed motifs in drug discovery.

Subject of Research: Rhodium-catalyzed stereoselective cyclopropanation of pyrroles to synthesize azabicyclic and azatricyclic nitrogen heterocycles

Article Title: Highly stereoselective synthesis of 2-Azabicyclo[3.1.0]hex-3-ene and 5-Azatricyclo[4.1.0.02,4]heptane scaffolds via Rh-catalyzed cyclopropanation of pyrrole

Article References: Ju, D., Zhao, C., Liu, B., Ma, J., Chi, S., & Zhao, J. (2026). Highly stereoselective synthesis of 2-Azabicyclo[3.1.0]hex-3-ene and 5-Azatricyclo[4.1.0.02,4]heptane scaffolds via Rh-catalyzed cyclopropanation of pyrrole. Journal of Saudi Chemical Society, 30(2), Article 26. https://doi.org/10.1007/s44442-026-00075-9

Image Credits: AI Generated

DOI: 10.1007/s44442-026-00075-9

Keywords: pyrrole, cyclopropanation, rhodium catalysis, cyclopropenes, 2-azabicyclo[3.1.0]hex-3-ene, 5-azatricyclo[4.1.0.0(2,4)]heptane, nitrogen heterocycles, stereoselectivity, medicinal chemistry, synthetic methodology, carbenoids, drug discovery

The new method, developed by Chengmi Huang, Dong Wu, Shiyang Wang, Yangyang Li and Guoyin Yin in the laboratory of Guoyin Yin, with computational contributions from Shuang Deng and Xiaotian Qi, is a sequential three-component coupling of alkynes, organohalides and a diboron reagent. Alkynes are attractive building blocks because they are flat, linear and readily available, and their conversion into substituted alkenes by adding two different groups across the triple bond, a process known as difunctionalization, is a powerful way to generate molecular complexity in a single operation. The difficulty has always been control: which group adds to which end of the alkyne, and whether the two groups end up on the same side or opposite sides of the resulting double bond.

Traditional approaches to alkyne difunctionalization typically rely on predesigned substrates bearing directing groups, or on rigid, single-pathway reaction mechanisms that lock in one regiochemical and stereochemical outcome. That rigidity restricts structural diversity, forcing chemists to redesign substrates and conditions every time a different isomer is needed. The Wuhan team’s solution is conceptually different. Instead of fixing the pathway, they exploit the fact that nickel catalysts can operate through two fundamentally different reactive intermediates, organometallic species on one hand and free radicals on the other, and they show that the choice of ligand determines which of these pathways dominates.

Mechanistic studies, combining experiments with density functional theory calculations, revealed the heart of the switch. The electronic properties of the ligand regulate whether the nickel catalyst generates an organometallic intermediate or a radical intermediate after oxidative addition of the organohalide. When the organometallic pathway prevails, the reaction proceeds through a well-defined nickel-carbon bond and delivers one set of alkene products; when radical generation dominates, the reaction follows an entirely different trajectory. Remarkably, the team found that the intrinsic metal-binding ability of the various radicals further modulates their reactivity, providing a second layer of selectivity control that governs how the radical interacts with the nickel-bound alkyne.

This dual-control architecture allows the researchers to access alkene products that are otherwise difficult to make. Under one set of conditions, the coupling delivers uncommon 1,2-trans alkenes, in which the two newly installed groups sit on opposite carbons of the double bond and point away from each other. Under another set of conditions, the same three components combine to give 2,1-cis alkenes, with the groups on adjacent carbons and on the same face. Achieving both regioselectivity and unique stereoselectivity simultaneously in a single catalytic operation is rare, and the fact that the outcome can be toggled by ligand choice rather than by rebuilding the substrate is what makes the system genuinely programmable.

The programmability extends beyond stereochemistry into molecular homologation. By controlling the incorporation of two alkyne units into the product, the team accomplished the divergent synthesis of conjugated diene homologues, molecules that differ by the number of conjugated alkene units in their backbone. Conjugated dienes are ubiquitous structural motifs: they appear in natural products such as the sorbicillinoid family, in agrochemicals including neonicotinoid insecticides, and in functional materials where the extent of conjugation dictates optical and electronic properties. Being able to prepare two different conjugated diene homologues from the same reaction setup, choosing between them with the catalyst rather than with new starting materials, offers a modular route to libraries of these valuable compounds.

The concept of radical sorting has been gaining momentum in catalysis research in recent years. Landmark studies from the MacMillan group on alkene dialkylation by triple radical sorting, and from other laboratories on cross-couplings enabled by bimolecular homolytic substitution, have shown that selectively channelling different radical species through a catalytic cycle can enable transformations that would otherwise be hopelessly scrambled. The Wuhan work pushes this idea further by sorting not just among radicals but between radical and organometallic regimes, effectively giving the chemist a switch that selects the reactive personality of the catalyst. The authors’ computational analysis, including average local ionization energy mapping of nickel(I) intermediates and buried-volume steric maps of the ligand environment, provided a quantitative picture of how ligand electronics and sterics steer the competition between pathways.

Detailed mechanistic experiments underpinned the proposal. The team examined how different ligands altered the fate of the alkenyl-nickel and alkenyl-radical intermediates that arise after the first addition across the alkyne, and their calculations compared the competing pathways for two distinct ligand frameworks, designated L4 and L6, at a high level of theory in solvents matching the experimental conditions. The results showed that chemoselectivity, whether the intermediate continues down the productive coupling channel or diverts into an unproductive one, is dictated by the interplay of ligand electronics and the radical’s affinity for the metal centre. This mechanistic clarity is valuable in its own right, because it converts what could have been an empirical observation into a set of design principles that other laboratories can apply to their own catalytic problems.

The practical scope of the method was demonstrated across a broad collection of substrates, with crystallographic data for seven representative products deposited at the Cambridge Crystallographic Data Centre to confirm the assigned structures unambiguously. The authors also showcased synthetic applications, including downstream transformations of the borylated alkene products and an application to the synthesis of histamine H3 receptor inverse agonists, a class of pharmacologically active compounds, illustrating how the reaction could feed directly into medicinal chemistry workflows. Because the products carry a boronate handle, they are primed for further diversification through well-established organoboron chemistry, multiplying the value of each coupling event.

The work was supported by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Shenzhen Science and Technology Program and institutional funds from Wuhan University, and it was peer reviewed by experts including Javier Corpas, Albert Poater and Qiuling Song. Beyond its immediate synthetic utility, the study signals a broader shift in how chemists think about selectivity. Rather than accepting the selectivity dictated by a substrate’s inherent bias, catalysts can now be engineered to override that bias and impose an outcome chosen by the operator. As switchable catalysis matures, the prospect of running a single reaction flask and extracting whichever molecular isomer a drug discovery or materials program requires, simply by swapping a ligand, moves from aspiration toward routine practice, and this nickel-catalysed alkene construction provides a compelling demonstration of that future.

Subject of Research: Ligand-switchable nickel catalysis for programmable regio-, stereo- and homologation-divergent construction of alkene skeletons from alkynes, organohalides and diboron reagents.

Article Title: Programmable alkene skeleton construction via switchable radical and organometallic sorting

Article References: Huang, C., Deng, S., Wu, D., Wang, S., Li, Y., Qi, X., & Yin, G. (2026). Programmable alkene skeleton construction via switchable radical and organometallic sorting. Nature Chemistry. https://doi.org/10.1038/s41557-026-02242-2

Image Credits: AI Generated

DOI: 10.1038/s41557-026-02242-2

Keywords: nickel catalysis, alkyne difunctionalization, radical sorting, organometallic chemistry, alkene synthesis, conjugated dienes, stereoselectivity, regioselectivity, ligand control, diboron reagent, homologation, synthetic methodology