A quirky photochemical process has become the latest addition to the toolbox for making alkenes, a process also known as olefination. The new reaction, reported independently by researchers in Germany and the US, stitches together two simple nitroalkane precursors to form crowded tri- and tetrasubstituted alkene products and addresses many of the limitations that plague established olefination reactions, the authors say (J. Am. Chem. Soc. 2026, DOI:10.1021/jacs.6c06459; J. Am. Chem. Soc. 2026, DOI: 10.1021/jacs.6c06460).
Alkenes are ubiquitous in organic chemistry, and generations of chemists have developed a raft of methods to install these double bonds across an impressive array of substrates and conditions. But classic reactions such as the Wittig, metathesis, the Julia, and the McMurry are often limited by harsh conditions, steric factors, or the requirement for specific structural features such as carbonyl groups. Because synthesizing crowded tri- and tetrasubstituted alkenes remains particularly challenging, there is a conspicuous gap in the scope of possible products.
Yet it was quite by chance that both teams stumbled on such an effective solution to this problem—an example of what the Nobelist David MacMillan calls “accelerated serendipity,” says Oliver Reiser, who led the team in Germany. The two groups were independently investigating the chemistry of α-nitroalkyl radicals—the single electron species generated from nitroalkanes—when they detected the formation of an alkene product under violet or blue light exposure. After several rounds of controls and repeats to confirm the observation, both teams set about optimizing their procedures and elucidating the underlying mechanism.
The sequence starts by deprotonating the nitroalkane to give a nitronate anion, but the two methods differ slightly in how this intermediate then initiates the reaction, says New York University’s Marvin Parasram, who led the US team. “In both our cases, though, we form an α-nitro radical that reacts with another nitronate coupling partner to form a C–C bond,” he says. “The resulting intermediate radical anion then goes through a single electron transfer event to eliminate NO2- and give the alkene product.” Each team demonstrated the photo-stitching process on a variety of nitroalkane substrates, generating a selection of di-, tri-, and tetrasubstituted alkenes, including a protected version of the cancer drug combretastatin A-4 and an analog of temarotene, an immunosuppressive drug.
But despite the methods’ similarities, they also complement each other, Reiser and Parasram say. The Reiser group’s ruthenium-mediated procedure yields predominantly tetrasubstituted products, while the Parasram team’s metal-free approach more effectively targets di- and trisubstituted alkenes. Operationally, the Reiser procedure is simpler, but the Parasram process uses milder conditions that tolerate a wider range of functional groups.
The teams have already established a collaboration to continue working on this reaction, and a key focus of their future work will be better understanding the specific niche for each procedure. “Each of them has advantages, and we want to understand better at what point you should use Marvin’s versus ours. For example, do we have a different scope or different selectivity?” Reiser says.
Method specifics aside, the wider approach could have valuable applications in medicinal chemistry and in the generation of compound libraries, says Michael Tilby. a synthetic chemist at the University of Bristol who was not involved in the work. “It’s a very nice way to produce these tetrasubstituted and trisubstituted species—it’s not replacing a method, but it’s allowing complementary reactivity with other olefinations,” he says. A key question will be unpacking how the different reaction conditions affect the final configuration of the molecule, Tilby adds. “It would be really nice to see whether future developments can introduce more stereocontrol into these reactions.”
