Writing in Nature, Minjie Zhao, Reisel Millán, Patricia Concepción, Avelino Corma and colleagues describe a catalyst in which subnanometre clusters of rhodium(III) oxide are confined inside the straight and zigzag channels of an MFI-type zeolite — the framework family best known as ZSM-5. The material, labelled KRh@MFI, looks deceptively simple: potassium-exchanged zeolite, a trace of rhodium, and nothing else. Yet under reaction conditions the confined Rh2O3 clusters are not passive containers of metal. Spectroscopic evidence collected during catalysis shows that they disrupt into isolated rhodium ions in two oxidation states, Rh3+ and Rh+, each sitting within the zeolite’s microporous architecture and each with its own catalytic personality.

That personality split is the heart of the discovery. Density functional theory calculations, cross-checked against infrared and X-ray absorption spectroscopy, indicate that hydroformylation at Rh3+ centres is energetically comparable to the pathway at Rh+ centres — both can plausibly convert an alkene, syngas and hydrogen into aldehyde. But the two sites differ sharply in what else they do. Rh+ is intrinsically prone to double-bond isomerization, the side reaction that migrates the C=C bond along the hydrocarbon chain. Isomerization is not a cosmetic nuisance: once an α-olefin such as 1-decene wanders into an internal position, subsequent hydroformylation yields a mixture of aldehydes whose linear fraction collapses. Rh3+, by contrast, is intrinsically more selective for hydroformylation and markedly less inclined to shuffle double bonds.

The Valencia group then did something chemically elegant: rather than trying to synthesize a material containing only Rh3+, they let both species coexist and selectively silenced the troublesome one. Small nitrogen-containing molecules — N-methylpyrrolidine (MP) and 1-methyl-2-pyrrolidone (NMP) — were fed alongside the reactants. These additives preferentially coordinate to the Rh+ sites inside the MFI channels, capping them like molecular plugs. The Rh+ isomerization function is thereby suppressed, while the Rh3+ sites remain catalytically accessible for hydroformylation. In effect, the researchers used a reversible, molecule-sized switch to convert a mixed-site catalyst into a single-function one, without any change to the solid itself.

The numbers that emerge from this strategy are extraordinary. With NMP as the additive, the catalyst delivers a linear-to-branched aldehyde ratio of 817 — a state-of-the-art figure — together with 96% selectivity to the linear aldehyde undecanal at 99.8% conversion of 1-decene. For a heterogeneous catalyst operating without phosphine ligands, these values rival or exceed what homogeneous industrial systems achieve, and they do so with a metal that is immobilized inside a robust inorganic framework rather than dissolved in the product stream. The work builds on the group’s earlier demonstration of low-temperature ethylene hydroformylation over phosphorus-stabilized rhodium sites in a one-pot-synthesized Rh-(O)-P-MFI zeolite, published in Nature Communications in 2023, and on a 2024 Nature paper reporting regioselective propene hydroformylation over rhodium-zeolite catalysts.

Characterization was as central to the study as catalysis. X-ray absorption spectroscopy performed at the CLÆSS beamline of the ALBA synchrotron allowed the team to track the oxidation state and coordination environment of rhodium under reaction conditions, distinguishing Rh3+ from Rh+ and confirming that the subnanometre oxide clusters fragment into isolated ions once the reaction atmosphere takes hold. Aberration-corrected electron microscopy at the University of Cádiz — high-angle annular dark-field scanning transmission electron microscopy and integrated differential phase-contrast imaging — provided direct visualization of the atomic dispersion within the zeolite channels. Infrared spectroscopy with carbon monoxide as a probe molecule, a technique with a long pedigree in rhodium-zeolite chemistry, helped fingerprint the individual site types.

The DFT analysis went beyond confirming feasibility. By mapping the energetics of the hydroformylation cycle at both Rh3+ and Rh+ centres, the calculations rationalized why the higher oxidation state favours formylation over isomerization: the electronic structure of Rh3+ stabilizes the key hydride-carbonyl intermediates along the aldehyde-forming pathway while disfavouring the alkyl intermediates that lead to double-bond migration. The apparent activation energies measured experimentally for hydroformylation and for isomerization, with and without MP present, matched this picture — the additive raised the barrier for the isomerization pathway far more than for the hydroformylation pathway, exactly as a site-blocking mechanism predicts.

Practicality matters as much as selectivity, and the team addressed it on two fronts. Recyclability experiments showed that the catalyst maintains its performance over repeated batches, an essential requirement for any solid that hopes to displace a homogeneous process. More significantly, the reaction was demonstrated in a semicontinuous operation mode, in which the solid catalyst remains in the reactor while reactants and products flow through — the configuration that industry would actually use. The additive strategy also proved tunable: beyond MP and NMP, the researchers screened a family of organic molecules including fluorinated and brominated variants, mapping how molecular structure governs the preference for Rh+ versus Rh3+ coordination.

The demonstration was not limited to a single substrate. The paper reports state-of-the-art results across a homologous series of C6 to C10 α-olefins, the linear terminal alkenes that serve as feedstocks for plasticizer alcohols and detergent precursors. Extending the record l/b ratio across this range suggests the site-isolation and additive-blocking strategy is a general principle rather than a peculiarity of one hydrocarbon chain length. Because α-olefin hydroformylation underpins a substantial fraction of global aldehyde production, even incremental selectivity gains translate into large savings in separation energy and raw material consumption; a jump to l/b ratios in the hundreds is in a different category altogether.

What the study ultimately offers is a design philosophy: instead of fighting to make every catalytic site identical, one can exploit the coexistence of site types and use small, reversible ligands to switch off the undesired function while the desired one keeps working. It is a strategy that echoes how enzymes use allosteric effectors, here transposed onto an industrial zeolite catalyst with nothing more exotic than a lactam solvent additive. If the approach generalizes to other metals, frameworks and reactions, the phosphine ligands that have defined hydroformylation since Otto Roelen’s era may finally face a credible heterogeneous challenger — one whose active sites are counted in single ions and whose selectivity is written into the walls of a zeolite.

Subject of Research: Regioselective hydroformylation catalysed by Rh3+ ions stabilized in an MFI zeolite

Article Title: Rh3+ stabilized in KRh@MFI catalyses regioselective hydroformylation

Article References: Zhao, M., Millán, R., Skorynina, A., Simonelli, L., Haro, M. L., Calvino, J. J., Concepción, P., & Corma, A. (2026). Rh3+ stabilized in KRh@MFI catalyses regioselective hydroformylation. Nature. https://doi.org/10.1038/s41586-026-11136-9

Image Credits: AI Generated

DOI: 10.1038/s41586-026-11136-9

Keywords: hydroformylation, rhodium, zeolite, MFI, regioselectivity, heterogeneous catalysis, single-site catalysts, DFT, olefins, N-methylpyrrolidone, aldehydes, catalyst selectivity

The stakes are enormous. Many of the most biologically active molecules in medicine and agriculture exist as two enantiomers, mirror-image structures that can behave completely differently in living systems. One form of a drug may heal while the other causes harm, which is why regulatory agencies and pharmaceutical manufacturers demand enantiomerically pure products. Asymmetric catalysis answers that demand by using chiral metal complexes to steer bond formation toward one stereoisomer with high stereoselectivity, enantioselectivity, and regioselectivity. The field traces its origins to 1968, when Knowles and Horner, together with their coworkers, performed the first asymmetric catalytic reaction. Since then, the interplay between metal identity and ligand design has defined progress across pharmaceuticals, agrochemicals, and medicinal chemistry.

At the heart of the review sits BINAP, or 2,2′-bis(diarylphosphino)-1,1′-binaphthyl, the landmark chiral ligand discovered by Ryoji Noyori and Hidemasa Takaya. BINAP supplies axial chirality, conformational flexibility, and strong steric and electronic asymmetry, and its complexes with ruthenium and rhodium catalyze an extraordinarily broad set of hydrogenations of olefins, ketones, and allylic alcohols with enantioselectivities that typically exceed ninety percent. The review emphasizes that these catalysts combine large turnover numbers with practical scalability, a combination that has made them workhorses in the industrial production of medicines and derivatives of natural products. Precise stereochemical control, the authors stress, emerges from the conjunction of ligand design, catalyst-substrate interactions, and carefully tuned reaction conditions rather than from any single factor.

One particularly striking line of research surveyed involves rhodium nanoparticles stabilized by chiral BINAP ligands, prepared in a one-pot synthesis alongside their silica-supported analogues. Characterization by transmission electron microscopy, phosphorus-31 magic-angle spinning NMR, and infrared spectroscopy of adsorbed carbon monoxide revealed highly dispersed nanoparticles with narrowly distributed core sizes. In the asymmetric hydroformylation of styrene, the chiral stabilization of the nanoparticle surface produced a regioselectivity of 99:1 and enantioselectivities of up to fifty-nine percent, markedly outperforming conventional systems. The chelated (R)-BINAP ligand carves out a rigid chiral pocket on the nanocatalyst surface, demonstrating that chirality can be effectively imposed even on nanoparticulate metal clusters.

The review also dissects how counterions, often dismissed as chemical spectators, reshape the behavior of rhodium-BINAP hydrogenation catalysts. Combining single-crystal X-ray crystallography, NMR spectroscopy, and catalytic testing, researchers showed that different counterions yield distinct pseudo-first-order rate constants and enantioselectivities, and that solvent choice further modulates both kinetics and selectivity. Intriguingly, for the hydrogenation of dimethyl itaconate in propylene carbonate, the anion exerted no effect at all on either activity or enantioselectivity, underscoring that counterion influence is complex and substrate-dependent. Alongside this, ruthenium(II)-BINAP complexes, notably Ru(CH3COO)2[(R)- or (S)-BINAP], achieve nearly quantitative yields of saturated isoquinoline alkaloid precursors from 2-acyl-1-alkylidene-1,2,3,4-tetrahydroisoquinolines with high optical purity—and, remarkably, in the stereochemical sense opposite to that delivered by the analogous rhodium catalyst, a reversal that highlights how metal identity alone can flip asymmetric induction.

Beyond phosphines, the review turns to the oxazoline family, where bis-oxazoline ligands have earned a reputation for delivering good to high enantioselectivities across many catalytic asymmetric reactions. New C2-symmetric Isbut-Box ligands, synthesized from substituted bis(oxazolin-2-yl)methylpropene frameworks, were evaluated in copper(I)-catalyzed cyclopropanation of olefins, with density functional theory calculations illuminating solvent effects and the structure of the copper(I) complex. These systems achieve up to seventy percent enantioselectivity and seventy-two percent diastereoselectivity, while a copper complex derived from a tert-butyl bisoxazoline showed promising activity in the enantioselective cyclopropanation of styrene. The authors note that the enormous early promise of bis-oxazolines has spurred extensive modification of the framework, including stiff, cyclic 1,4-box backbones in both C2- and C1-symmetric variants designed to tighten stereochemical control further.

Oxazolines are also proving valuable beyond traditional solution-phase transformations. C2-symmetric bis(oxazoline) ligands serve as transient chiral auxiliaries for constructing enantiomerically pure bis-cyclometalated rhodium(III) complexes, which act as configurationally stable stereogenic catalysts in asymmetric photocatalysis. Using inexpensive beta-amino alcohols and a symmetrically disubstituted diethyl malonimidate salt, the chiral auxiliary complexes formed within a single hour at room temperature. In a parallel effort, a new class of triazolyl-oxazoline ligands combining a chiral 2-oxazoline with a 1,2,3-triazol-4-yl moiety was shown by X-ray diffraction to coordinate palladium(II) either as monodentate ligands through the oxazoline nitrogen or as N,N-chelators, generating cationic allyl complexes, neutral dimers, and mononuclear dichloro species—an adaptable coordination chemistry that widens the design space for chiral palladium catalysis.

Perhaps the most forward-looking section concerns BINOL, 1,1′-bi-2-naphthol, paired with abundant main-group metals. Recent work revealed an unusual chiral-at-metal mechanism in BINOL-aluminum asymmetric catalysis: an octahedral chiral aluminum complex, thermodynamically more favorable than the previously proposed aluminum hydride, operates through ligand-assisted hydride transfer. In the catalytic hydroboration of heteroaryl ketones with pinacolborane, the optimized conditions delivered ninety-nine percent yield and ninety-nine percent enantiomeric excess, producing chiral alcohols prized in pharmaceutical synthesis. Meanwhile, bifunctional BINOL and H8BINOL ligands catalyze the addition of diphenylzinc to aldehydes at room temperature without additives, and a related ligand promotes highly enantioselective TMSCN additions when combined with Me2AlCl, with yields spanning seventy-five to ninety-six percent across optimized solvent systems.

The review closes with bis(imine) systems, where a bidentate chiral bis(imine)-copper(II) triflate complex drives the 1,3-dipolar cycloaddition of nitrones to electron-deficient dipolarophiles with endo/exo ratios of up to 95:5 and enantioselectivities reaching ninety-nine percent—performance that outshines established TADDOL-titanium, bis-oxazoline magnesium, and BINAP-palladium systems for this transformation. Together, the authors argue, these results show that rational ligand design and metal-ligand cooperation are the twin engines of progress in asymmetric catalysis. They call for sustainable synthesis built on eco-friendly oxidants, solvents, and reaction conditions, and for deeper integration of mechanistic studies and computational chemistry to design the next generation of rigid, electronically tunable chiral catalysts capable of tackling the most demanding reactions in organic synthesis.

Subject of Research: Innovative chiral metal ligand architectures for asymmetric catalysis

Article Title: Review on innovative metal ligand architectures for asymmetric catalysis

Article References: Patel, S. P., Shaikh, R. S., Patel, N. C., & Savant, S. S. (2026). Review on innovative metal ligand architectures for asymmetric catalysis. Discover Green Chemistry, 1(1), Article 32. https://doi.org/10.1007/s44509-026-00035-x

Image Credits: AI Generated

DOI: 10.1007/s44509-026-00035-x

Keywords: asymmetric catalysis, chiral ligands, BINAP, BINOL, bis-oxazoline, enantioselectivity, hydrogenation, hydroformylation, rhodium nanoparticles, green chemistry, homogeneous catalysis, cyclopropanation