2 ways to stick nitrogen into alkenes

Reactions that completely break carbon-carbon double bonds have particular transformative power in synthesis. Ozonolysis, which splits one alkene into two carbonyl compounds using trioxygen, is widely used in both industrial and academic settings. And while nitrogen is a valuable component of many natural products, drugs, and agrochemicals, chemists have struggled to come up with an accessible nitrogen-based equivalent to ozonolysis.

Now, two teams of chemists working independently have each come up with a new approach to filling the nitrogen-sized hole in the alkene cleavage toolbox. Both methods break carbon-carbon double bonds and install carbon-nitrogen bonds, and both accept a broad collection of starting materials, including natural products, but they work differently and give different products. 

Bill Morandi’s group at Swiss Federal Institute of Technology (ETH), Zurich, devised an approach that uses an iodine oxidant and ammonium carbamate to turn linear alkenes into nitriles and branched alkenes into amidines (Science 2025 DOI: 10.1126/science.adq4980). 

Yannick Brägger, a PhD student in Morandi’s lab, says he was searching for new reactivity that might provide a more general way to cleave carbon bonds and install nitrogens. He dug into the scientific literature, where he found a 1969 paper about breaking open three-sided nitrogen-containing rings to give carbonyl products. He thought if he could form those rings from alkenes, he could get to the cleavage products he sought. After some experimentation, he found a way to do pretty much exactly that.

Meanwhile, Ning Jiao and his team at Peking University split alkenes into a nitrile and a ketone using an azide reagent, molecular oxygen, and a zeolite-supported copper catalyst (Science 2025 DOI: 10.1126/science.adq891). The reaction builds on work the group did over a decade ago (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja403824y) using an organic radical catalyst to do basically the same transformation. This revamped version offers an expanded scope and a recyclable catalyst.

Jiao says he hopes to build the foundation for a “practical and selective approach” to double-bond cleavage that complements established approaches such as ozonolysis. He adds that he and his team are continuing to work on understanding the copper-catalyzed reaction and incorporating less expensive nitrogen sources.

A key feature that each group highlighted is its method’s ability to transform natural products. “It's a dream for every synthetic chemist” to be able to use cheap, chiral terpenes as a basis for complex synthesis, Brägger says. Turning terpenes into chiral amidines provides easy access to valuable chiral nitrogen-containing building blocks. Jiao’s team also explored numerous examples of snipping double bonds in complex terpenoids, steroids, and glycals.

Ohyun Kwon, an organic chemist at the University of California, Los Angeles, who was not involved in either study, says that neither approach is perfect but each has its strengths. For example, Jiao’s method is catalytic. And although Morandi’s isn’t, it uses commercially available reagents as opposed to Jiao’s bespoke catalyst. Overall, Kwon says that she considers both papers “a development in the right direction” and that she is always in favor of new and unconventional ways to manipulate compounds with double bonds. “Being able to achieve what was not possible, that's something that we should celebrate.”