The motivation behind the work stems from a striking imbalance in the field. Carbonylative Sonogashira couplings, first demonstrated by Tanaka and coworkers in 1981, have been applied to an impressive range of substrates over the past four decades, including aryl and vinyl triflates, aryl iodides, aryl bromides, alkyl halides, benzyl chlorides, aryl triazenes, and even diazonium salts, with formic acid serving as a carbon monoxide surrogate in the latter case. More recently, aryl thianthrenium salts have opened the door to direct, selective functionalization of aromatic carbon-hydrogen bonds. Yet despite this breadth, arene derivatives have been used almost exclusively as substrates. Given the synthetic utility of alkenyl-alkynyl ketones, the Hungarian research team set out to ask whether iodoalkenes could serve as competent partners, and to map the structure-reactivity and structure-selectivity relationships that govern these transformations.

The investigation began with the direct Sonogashira coupling, using 2-iodobornene as a sterically demanding model iodoalkene and phenylacetylene as the coupling partner. The catalytically active palladium(0) species was generated in situ from palladium(II) acetate and a phosphine ligand, with copper(I) iodide as co-catalyst. As is common in Sonogashira chemistry, an unwanted side reaction loomed: the Glaser homocoupling of the terminal alkyne, which in this case produced 1,4-diphenyl-1,3-butadiyne. Optimizing the reaction therefore meant balancing conversion against selectivity toward the desired enyne product, a delicate dance of solvent, base, ligand, and stoichiometry.

The optimization data reveal how sensitive these couplings are to reaction conditions. In tetrahydrofuran with triphenylphosphine as ligand, conversions hovered around 35 to 37 percent regardless of whether 1.1 or 1.5 equivalents of alkyne were used. Switching the base from triethylamine to potassium carbonate pushed the selectivity toward the enyne to a perfect 100 percent, while omitting the phosphine ligand altogether collapsed the conversion to a mere 12 percent, underscoring its necessity. The decisive breakthrough came with the bidentate ligand Xantphos, which lifted conversion to 72 percent while maintaining complete selectivity. Dimethylformamide, a solvent widely used in such couplings, kept conversion high but came at a steep cost: selectivity plummeted, and with inorganic base the reaction produced essentially none of the desired enyne, the diyne by-product dominating instead.

With the optimized conditions in hand, the team explored the substrate scope across six structurally diverse iodoalkenes, including 2-iodobornene, 1-iodocyclohexene, 1-iodo-4-tert-butylcyclohexene, 1-iodocyclopentene, trans-1-iodo-1-octene, and 17-iodo-androst-16-ene, a steroid-derived substrate. These were paired with five terminal alkynes: phenylacetylene, 1-hexyne, 3-hydroxy-1-butyne, trimethylsilylacetylene, and ethynylferrocene. The resulting conjugated enynes were isolated in moderate to good yields. Aryl alkynes generally outperformed their aliphatic counterparts, while trimethylsilylacetylene consistently delivered the lowest yields across the iodoalkene series. Steric effects were clearly at play, as the more hindered iodoalkenes gave lower yields with bulky alkyne partners. Intriguingly, the hydroxy-functionalized alkyne proved highly effective, particularly with the parent iodoalkene, hinting that substrate-specific effects can override simple reactivity expectations.

The carbonylative variant, the true centerpiece of the study, introduces carbon monoxide as a one-carbon synthon into the catalytic cycle. Under atmospheric pressure of CO, the alkenyl-palladium species formed after oxidative addition undergoes CO insertion to generate an acyl-palladium intermediate, which is then trapped by the alkynyl nucleophile to yield an alkynyl ketone bearing both alkenyl and alkynyl fragments. These alkenyl-alkynyl ketones are valuable building blocks, and accessing them from iodoalkenes under mild conditions represents a meaningful addition to the synthetic repertoire. The optimization, however, revealed an even greater sensitivity to the solvent-base combination than the direct coupling.

In dimethylformamide with potassium carbonate, conversions climbed rapidly, reaching 100 percent within three hours, but the direct Sonogashira product and the carbonylative product formed in nearly equal amounts, an unacceptable outcome for chemoselectivity. Replacing the inorganic base with triethylamine slowed the reaction at short times but dramatically improved selectivity toward the alkynyl ketone; at complete conversion after six hours, the ratio of carbonylative product to direct coupling product to diyne stood at an impressive 89 to 9 to 2. Tetrahydrofuran with triethylamine fared far worse, delivering only partial conversion even after 24 hours while the proportion of non-carbonylative and homocoupled by-products steadily grew. Dimethylformamide with triethylamine was therefore selected as the standard for preparative work.

Applying these conditions across the full substrate matrix yielded alkenyl-alkynyl ketones in yields ranging from 19 to 92 percent. Sterically hindered iodoalkenes again lagged behind with the bulky ethynylferrocene partner, while 1-hexyne proved an especially willing participant, its acylation by the acyl-palladium intermediate being more favorable than that of the other alkynes. Not every alkyne cooperated, however. Trimethylsilylacetylene, a reliable partner in many coupling chemistries, took an unexpected detour under the carbonylative conditions: instead of the desired silylated alkynyl ketone, desilylation occurred, followed by addition of diethylamine generated from the triethylamine-containing medium, producing a beta-diethylamino enone or enaminone-type by-product. Switching to potassium carbonate only partially suppressed this pathway and triggered additional side reactions, including a doubly coupled product and a dimethylamino compound derived from dimethylformamide itself, as confirmed by gas chromatography-mass spectrometry. The authors concluded that trimethylsilylacetylene is not a generally reliable partner for the carbonylative protocol under these conditions.

The analytical rigor underpinning the study deserves note. Reaction progress was monitored by gas chromatography with dodecane as an internal standard, using a carefully calibrated single-point relative response factor for the model iodoalkene. Structural assignments rested on nuclear magnetic resonance spectroscopy recorded on a 500-megahertz instrument, complemented by mass spectrometry and infrared spectroscopy with attenuated total reflectance sampling. All isolated compounds were fully characterized, and where products had been reported previously, the analytical data matched the literature values, lending confidence to the reported yields and selectivities.

Taken together, the findings establish iodoalkenes as genuinely useful substrates for accessing two complementary product classes under mild palladium catalysis: conjugated enynes from the direct reaction, performed with a palladium acetate, Xantphos, and copper iodide system in tetrahydrofuran with potassium carbonate, and carbonylated enynone-type products from the carbonylative variant in dimethylformamide with triethylamine under atmospheric carbon monoxide. The study demonstrates that reaction outcome is governed by an interplay of solvent and base, the steric demand of the iodoalkene, and the nature of the terminal alkyne. The successful use of ethynylferrocene as a redox-active alkyne partner adds an intriguing dimension for future materials-oriented applications, while the trimethylsilylacetylene limitation offers a candid map of the protocol’s boundaries. For a transformation whose aryl halide chemistry has been exhaustively catalogued, this systematic exploration of the alkenyl frontier shows that even forty-year-old catalytic reactions still hold surprises worth pursuing.

Subject of Research: Palladium-catalyzed direct and carbonylative Sonogashira coupling reactions of iodoalkenes with terminal alkynes

Article Title: Direct and carbonylative Sonogashira reactions of iodoalkenes

Article References: Jenei, L. B., Zugó, A., Mikle, G., & Kollár, L. (2026). Direct and carbonylative Sonogashira reactions of iodoalkenes. Results in Chemistry, 31, Article 103924. https://doi.org/10.1016/j.rechem.2026.103924

Image Credits: AI Generated

DOI: 10.1016/j.rechem.2026.103924

Keywords: Sonogashira coupling, carbonylation, iodoalkenes, palladium catalysis, cross-coupling, alkynyl ketones, enynes, Xantphos, carbon monoxide, terminal alkynes, homogeneous catalysis, synthetic chemistry

The challenge the team set out to solve is one of the deepest in catalysis. Ethane, the second-largest component of natural gas, is held together by carbon–hydrogen bonds that are among the least reactive in chemistry. Breaking one of these bonds selectively, and then persuading the resulting fragment to bond with a carbon monoxide molecule rather than simply burning to carbon dioxide or over-oxidizing into a soup of byproducts, has defeated generations of catalyst designers. Conventional approaches rely on high temperatures that push reactions toward complete combustion, destroying precisely the selectivity that makes a process commercially attractive.

The new work, led by Qi Lu of Tsinghua University together with Bingjun Xu of Peking University and Mu-jeng Cheng of National Cheng Kung University, sidesteps this problem by splitting the catalytic labor between two distinct chemical roles of the same metal. Adsorbed oxygen species on an oxidized copper surface are responsible for activating ethane, abstracting a hydrogen atom to create a surface ethyl species. Meanwhile, copper ions released from the surface oxide into the acidic solution form carbonyl species with dissolved carbon monoxide, and it is at the interface between these two worlds that the crucial carbon–carbon bond forms.

Carbon monoxide plays a double role in this scheme, and that dual function is central to the reaction’s unusual selectivity. It serves as the C1 building block that is inserted into the ethane-derived fragment, ultimately delivering the carboxylic acid functionality of propionic acid. But it also acts as a selectivity-directing agent, intercepting the reactive ethyl intermediates before they can drift into unproductive oxidation pathways. By capturing the C–H activation intermediate quickly, CO essentially funnels the chemistry toward a single desired product rather than the mixture of alcohols, aldehydes and acids that typically plagues partial oxidation of light alkanes.

The experimental evidence for this mechanism is unusually thorough. The team used isotopic labelling to confirm that both the two-carbon skeleton of the product derives from ethane and the single added carbon from carbon monoxide, ruling out alternative carbon sources. In situ surface-enhanced infrared and Raman spectroscopies, techniques the group has refined in earlier studies of carbon monoxide electroreduction on copper, allowed the researchers to watch copper carbonyl species and surface ethyl intermediates directly on the working catalyst. Density functional theory calculations performed by the Cheng group in Tainan provided the energetic underpinning, showing that interfacial coupling between the copper carbonyl and the ethyl species is feasible under the mild conditions of the experiment.

The performance numbers tell a story of deliberate trade-offs. At propionic acid formation rates of up to 120 micromoles per gram of copper per hour, the selectivity settles at around 50 percent. When the team tuned conditions to slow the rate, selectivity climbed to its optimum of 83 percent, indicating that the competing pathways can be suppressed at the cost of throughput. This rate–selectivity relationship is a familiar feature of partial oxidation chemistry, but the fact that both ends of the trade-off are respectable at ambient temperature is what distinguishes the result. The researchers suggest that the strategy establishes CO-mediated alkane carbonylation under mild conditions as a genuine synthetic platform for organic acid production.

The intellectual lineage of the work stretches back decades. Carbonylation, the insertion of carbon monoxide into metal–carbon bonds, is the backbone of some of the largest industrial processes on Earth, most famously the methanol-to-acetic acid route that feeds global demand for one of the most important commodity chemicals. Applying carbonylation to saturated hydrocarbons, however, has required either superacidic media, precious metal catalysts or harsh temperatures. Early hints came from work in the 1970s showing that copper(I) carbonyl cations could carbonylate saturated hydrocarbons in strong acids, and more recent studies have explored carbonylation of alkanes over zeolites and via photocatalytic hydrogen atom transfer. The new study brings these threads together in a heterogeneous, aqueous system that operates at room temperature.

Copper’s starring role is itself notable. The metal has enjoyed a renaissance in catalysis over the past decade, particularly in electrochemistry, where oxide-derived copper electrodes proved capable of converting carbon dioxide and carbon monoxide into multicarbon products such as ethanol and acetate. That literature established that copper carbonyl species on oxidized copper surfaces can engage in carbon–carbon bond formation, and the present work transplants that insight from electrochemistry into a purely chemical, oxygen-driven setting. The researchers’ earlier investigations into how carbon monoxide coverage governs coupling on copper surfaces clearly informed the design of the new reaction, illustrating how mechanistic understanding in one field can seed breakthroughs in another.

The sustainability implications are considerable. Ethane is abundant, cheap and often flared or simply burned as fuel in regions far from petrochemical infrastructure. Converting it directly into propionic acid, a preservative, feed additive and chemical intermediate currently produced largely through petrochemical routes, would add value to a stranded resource while avoiding the energy intensity of steam cracking or high-temperature oxidation. Running the reaction in dilute acid with molecular oxygen as the terminal oxidant, rather than stoichiometric oxidants or precious metals, keeps the reagent palette inexpensive and environmentally benign. The authors acknowledge that the current rates, while scientifically impressive, remain far from industrial scale, and that catalyst durability and reactor engineering will need attention before any commercial translation.

What makes the result resonate beyond its immediate application is the demonstration that the most inert bonds in organic chemistry can be tamed at ambient conditions when activation and functionalization are assigned to different, cooperating chemical environments on a single catalyst. The interfacial coupling concept, in which a surface-bound alkyl fragment meets a solution-phase carbonyl species precisely at the boundary between oxide and liquid, offers a design principle that could extend to methane, propane and other light alkanes. If the strategy generalizes, the humble copper surface, working quietly at room temperature, may become the stage on which natural gas is rewritten into the building blocks of the chemical industry.

Subject of Research: Room-temperature catalytic coupling of ethane and carbon monoxide to synthesize propionic acid over copper

Article Title: Propionic acid synthesis via room-temperature coupling of ethane and CO

Article References: Hou, J., Liu, W., Wang, K.-H., Li, M., Wen, S.-C., Cheng, M.-J., Xu, B., & Lu, Q. (2026). Propionic acid synthesis via room-temperature coupling of ethane and CO. Nature Synthesis. https://doi.org/10.1038/s44160-026-01168-4

Image Credits: AI Generated

DOI: 10.1038/s44160-026-01168-4

Keywords: catalysis, copper catalyst, ethane, carbon monoxide, propionic acid, carbonylation, C–H activation, selectivity, mild conditions, organic acids, sustainability, heterogeneous catalysis