The difficulty lies in how aziridines are activated. In classical approaches, chemists attach strongly electron-withdrawing groups such as tosyl or nosyl to the ring nitrogen. These groups weaken the carbon-nitrogen bonds, making the ring susceptible to attack by nucleophiles or to activation by transition metals. The problem is that the activating group must then be stripped away and replaced with the desired N-substituent, typically through alkylation or reductive amination, adding steps, waste and cost to every synthesis. For N-alkyl aziridines, which already carry the nitrogen substituent one actually wants, this detour is impossible by definition, and the rings have remained essentially inert under established transition-metal catalytic manifolds.

The Leonori group’s solution, published in Nature Chemistry, begins with a simple Lewis acid-base interaction. Borane, BH3, coordinates to the nitrogen atom of the aziridine, forming a stable aziridine-ligated borane complex. This complex can then be converted into an aziridine-ligated boryl radical, a species in which the unpaired electron sits on the boron centre. That radical undergoes a regioselective beta-scission, cleaving the more substituted carbon-nitrogen bond and releasing the strain of the three-membered ring to generate a beta-aminoalkyl radical. Crucially, this radical intermediate is exactly the kind of species that modern cross-coupling catalysis is built to capture.

The idea has deep roots. In pioneering low-temperature electron paramagnetic resonance studies, Brian Roberts and colleagues showed decades ago that amine-borane complexes could undergo hydrogen-atom abstraction to form amine-ligated boryl radicals, which rapidly fragmented across the aziridine ring. But that reactivity had never been exploited synthetically. The Aachen team recognised that if the fragmentation could be tamed and the resulting radicals funnelled into catalytic cross-couplings, the entire activating-group economy of aziridine chemistry could be rewritten.

Before running a single reaction, the researchers turned to computation to interrogate a subtle stereochemical hazard. Because the aziridine nitrogen is pyramidalised in the borane complex, two diastereomeric boryl radicals, trans and cis, can form. Roberts’ data had suggested these diastereomers fragment across different carbon-nitrogen bonds, which threatened to produce messy mixtures of regioisomeric products. The team’s calculations, performed at the UM06-2X/def2-QZVP level with solvation corrections, told a more encouraging story. For aziridines bearing a beta-phenyl substituent, both diastereomers fragment with complete regioselectivity toward the stabilised benzylic radical, in processes that are highly exothermic and essentially barrierless. For beta-alkyl substrates the picture is more nuanced: the trans diastereomer selectively delivers the desired secondary radical, aided by favourable orbital overlap between the boryl radical’s singly occupied molecular orbital and the sigma-star orbital of the more substituted carbon-nitrogen bond, while the cis isomer risks promiscuous cleavage. Fortunately, borane coordination was found to deliver the trans diastereomer exclusively or predominantly in practice.

With the mechanism mapped, the team built two complementary catalytic platforms. The first is an oxidative copper system. A copper(I) catalyst reacts with a silyl peroxide oxidant, cumylO2TMS, to generate an electrophilic cumyloxyl radical. This radical performs a polarity-matched hydrogen-atom abstraction on the aziridine-borane complex, forging the boryl radical that fragments to the beta-aminoalkyl radical. Meanwhile, a nucleophile such as an aryl boronic acid transmetalates with copper(II) to form an aryl-copper species that captures the radical. Reductive elimination, either through a discrete copper(III) intermediate or by direct carbon-carbon bond formation, delivers the beta-arylated product, which is unmasked to the free N-alkylamine during hydrolytic work-up. A clever design feature is that the arylated intermediate formed before work-up shields the alpha-nitrogen positions from further hydrogen abstraction, protecting the product from over-functionalisation under the oxidative conditions.

The scope of this copper manifold proved impressively broad. Using an N-propyl aziridine and phenylboronic acid as benchmarks, the team obtained the beta-phenylated amine in good yield, including on gram scale. Electron-rich and electron-poor para-substituted boronic acids, meta-substituted and disubstituted reagents, 2-naphthyl, benzofuranyl and even pyridyl boronic acids all coupled successfully. On the aziridine side, both electron-rich and electron-poor beta-aryl groups were tolerated, including a cyclobutane-annulated system, and the N-substituent could be methyl, hexyl, benzyl, isopropyl or cyclohexyl. The same catalytic blueprint also accepted other nucleophiles: trimethylsilyl cyanide delivered beta-nitrile amines, valuable because the nitrile can be hydrolysed to beta-amino acids, while diphenyl disulfide furnished beta-thioether derivatives in high yield, and proof-of-concept azidation and phthalimidooxylation reactions were also demonstrated.

Perhaps the most striking feature of the chemistry is its regioselectivity. In classical aziridine ring openings, the substrate dictates the outcome: benzylic systems cleave at the more substituted position to give branched products, whereas beta-alkyl systems prefer the less substituted bond and deliver linear products. Methods that override this intrinsic bias are exceedingly rare. The boryl radical fragmentation does exactly that, consistently cleaving the more substituted carbon-nitrogen bond across both beta-aryl and beta-alkyl substrates. Every substrate examined in the cyanation series, including derivatives based on the antiarrhythmic drug mexiletine, a glycine derivative, an atorvastatin intermediate and a medicinally relevant N-Boc-piperidinyl motif, delivered the branched product exclusively. Even an unsubstituted aziridine, proceeding through a primary radical, could be opened, and gem-disubstituted systems gave access to alpha,beta-difunctionalised amines and tertiary nitriles.

Where the copper system falters, a second platform picks up the slack. Beta-alkyl aziridines coupled only modestly under copper catalysis, so the team embedded the same hydrogen-atom abstraction and fragmentation steps into a dual photo-nickel manifold. Triplet-excited diaryl ketone photocatalysts, activated by purple light-emitting diodes, abstract the hydrogen atom from the borane complex, while a nickel catalyst handles the cross-coupling with aryl bromides, a widely available class of electrophilic partners. After oxidative addition of the aryl bromide to nickel(0), the beta-aminoalkyl radical is captured by the aryl-nickel(II) complex, and reductive elimination from the resulting nickel(III) intermediate delivers the product, with the ketyl radical by-product closing both catalytic cycles through single-electron transfer. This umpolung variant, pairing the aziridine with electrophiles rather than nucleophiles, lifted the yield of the model beta-alkyl arylation to 54 percent and tolerated a wide panel of aryl and heteroaryl bromides, including pyridyl and thiazole systems, although strongly electron-donating substituents and highly stabilised benzylic radicals proved limiting.

Together, the two manifolds offer chemists a choice of partner and catalyst matched to the radical at hand, all flowing from a single mechanistic blueprint. By eliminating the historical dependence on electron-withdrawing N-activating groups, the work streamlines access to beta-functionalised N-alkylamines, compounds that sit at the heart of countless bioactive molecules, and establishes aziridine-ligated boryl radicals as a genuinely useful class of synthetic intermediates. The Aachen team anticipates that the generality of the activation mode will accelerate the synthesis of biologically relevant targets and inspire broader exploration of amine-ligated boryl radicals, a reactivity logic that sat dormant in the literature for four decades before finally being put to work.

Subject of Research: Radical ring-opening and divergent functionalization of N-alkyl aziridines via aziridine-ligated boryl radicals

Article Title: Divergent ring opening and functionalization of N-alkyl aziridines via boryl radical fragmentation

Article References: Peng, P., Roure, B., Lulli, T., Stavagna, C., Lonardi, G., & Leonori, D. (2026). Divergent ring opening and functionalization of N-alkyl aziridines via boryl radical fragmentation. Nature Chemistry, 18(10), 1755-1762. https://doi.org/10.1038/s41557-026-02247-x

Image Credits: AI Generated

DOI: 10.1038/s41557-026-02247-x

Keywords: aziridines, boryl radicals, ring opening, copper catalysis, nickel catalysis, photocatalysis, cross-coupling, beta-aminoalkyl radicals, regioselectivity, borane coordination, organic synthesis, medicinal chemistry

The reaction at the heart of the study, cyclohexane ring opening, is far more than an academic curiosity. Naphthenic hydrocarbons such as cyclohexane and its alkylated relatives are abundant in the heavy fractions of crude oil, and their closed-ring structures give diesel fuels poor ignition quality, expressed as a low cetane number. Opening the ring converts these cyclic molecules into branched and linear paraffins with markedly better combustion behavior. In principle, a single C-C bond in cyclohexane, when cleaved under hydrogen, yields n-hexane, a straight-chain molecule that burns far more readily in a diesel engine. The challenge is doing this selectively, because the same metal surfaces that open rings can also chop the resulting chains into smaller fragments or trigger unwanted side reactions.

Rhodium has long attracted attention for this task. Among the noble metals tested for hydrogenolysis of naphthenes, rhodium displays a notable ability to cleave C-C bonds while leaving the desired linear products relatively intact, particularly when the metal is dispersed on the right support. Zirconia has emerged as an intriguing candidate support because of its amphoteric surface character, its thermal stability and the way it interacts electronically with deposited metals. Earlier work by some of the same authors had already demonstrated that the nature of the support strongly influences how rhodium catalysts perform in cyclohexane ring opening, which raised the natural follow-up question: does the method used to load the rhodium onto the zirconia matter just as much?

To answer it, the team prepared a series of catalysts, each containing one weight percent rhodium on zirconium dioxide, using four distinct synthesis strategies: wet impregnation, excess-solution impregnation, deposition of the metal by urea hydrolysis, and direct deposition of preformed rhodium nanoparticles. These methods differ subtly but importantly in how the metal precursor encounters the support surface. Wet impregnation floods the pores with a solution containing just enough metal to reach the target loading, while excess impregnation immerses the support in a larger volume of solution. Urea deposition-precipitation relies on the slow, homogeneous release of hydroxide ions to precipitate rhodium species gently across the surface, and nanoparticle deposition introduces the metal as preformed colloidal particles whose size is fixed before they ever touch the oxide.

Once the catalysts were made, the researchers subjected them to a battery of characterization techniques that reads like a tour of modern materials analysis. X-ray diffraction probed the crystal structure of the zirconia support and confirmed the phase composition of each sample. Scanning electron microscopy paired with energy-dispersive X-ray spectroscopy mapped the morphology and elemental distribution, while transmission electron microscopy, aided by fast Fourier transform analysis of the images, resolved the rhodium particles themselves. Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy interrogated the surface chemistry, with the latter revealing how much rhodium actually resides at the outermost surface where catalysis happens. Temperature-programmed reduction in hydrogen completed the picture by measuring how readily the oxidized rhodium species could be reduced to the metallic state.

Two findings from this characterization campaign stand out. First, in the temperature-programmed reduction experiments, every sample consumed more hydrogen than the stoichiometric amount needed to reduce the nominal rhodium oxide loading, a signal of extra hydrogen uptake that the authors attribute to hydrogen interacting with the support or with partially reduced species. The wet impregnation sample showed the highest hydrogen consumption of all, hinting at a particularly rich population of reducible surface species. Second, X-ray photoelectron spectroscopy revealed that the catalyst prepared by depositing preformed nanoparticles carried a much higher concentration of rhodium at the surface than its counterparts. That difference, metal sitting where the reactants can actually reach it, would prove decisive in the catalytic tests.

And decisive it was. When the catalysts were evaluated in cyclohexane hydrogenolysis, the nanoparticle-derived sample delivered the highest yield of n-hexane, reaching 17.3 percent at 325 degrees Celsius. Even more striking was its selectivity: at the milder temperature of 275 degrees Celsius, roughly 87 percent of the converted cyclohexane emerged as the desired n-hexane product. In a reaction network where ring opening competes with multiple hydrogenolysis pathways that fragment the molecule, a selectivity approaching nine parts in ten is a genuinely impressive figure. The result ties performance directly to surface accessibility, since rhodium buried inside the porous support or locked in poorly dispersed agglomerates contributes little to the reaction.

The broader lesson resonates well beyond this single reaction. In heterogeneous catalysis, the term structure sensitivity describes reactions whose rate and selectivity depend on the size and geometry of the metal particles. Rhodium nanoparticle size effects have been documented in processes ranging from carbon dioxide reforming of methane to steam reforming, and researchers have shown that atoms at corners and edges of metal nanocrystals can behave very differently from those on flat terraces. By fixing the metal as nanoparticles before deposition, the synthesis route effectively pre-selects the ensemble of surface sites that will do the catalytic work. The new study adds cyclohexane ring opening to the list of reactions where this pre-selection pays measurable dividends, and it does so with a practical implication: catalyst manufacturers can, in effect, tune selectivity by choosing how the metal is introduced.

There is also an energy-transition angle worth noting. Ring-opening chemistry is increasingly discussed in the context of upgrading not only fossil diesel streams but also hydrotreated oils from renewable and waste sources, where naphthenic rings are common. Catalysts that convert these rings selectively into high-cetane linear paraffins at moderate temperatures could improve fuel quality while minimizing hydrogen consumption and unwanted cracking. Zirconia-supported rhodium, with its combination of strong C-C bond activation and high n-hexane selectivity, fits that profile, and the demonstration that a deposition route maximizes surface rhodium concentration offers a concrete recipe for improvement.

Of course, a one-weight-percent rhodium catalyst built on a precious metal remains expensive for bulk fuel applications, and the authors note that no new datasets beyond the study itself were generated. Scaling the nanoparticle deposition approach, stabilizing the particles against sintering under industrial conditions, and exploring cheaper metals that mimic rhodium’s selectivity are the obvious next steps. But the core message of the work is clean and consequential: in catalysis, the recipe is part of the chemistry. Two catalysts with identical composition on paper can behave entirely differently in a reactor, and the difference traces back to decisions made in a beaker long before the first molecule of cyclohexane arrives. For a field racing to design catalysts rationally rather than by trial and error, that is a reminder worth repeating.

Subject of Research: Effect of synthesis method on Rh/ZrO2 catalysts for selective cyclohexane ring opening to n-hexane

Article Title: Rh/ZrO2 Catalysts for Cyclohexane Ring Opening: A Role of Synthesis Method

Article References: Abkhalimov, E. V., Ershov, V. A., Mashkin, M. Y., Kartavova, K. E., & Kustov, A. L. (2026). Rh/ZrO2 Catalysts for Cyclohexane Ring Opening: A Role of Synthesis Method. Catalysis Letters, 156(10), Article 286. https://doi.org/10.1007/s10562-026-05524-z

Image Credits: AI Generated

DOI: 10.1007/s10562-026-05524-z

Keywords: rhodium, zirconia, cyclohexane, ring opening, heterogeneous catalysis, nanoparticles, hydrogenolysis, cetane number, fuel upgrading, catalyst synthesis, XPS, selectivity