Zhou Qilin's team publishes again in JACS, with the expression CMS-L mass spectrometer helping achieve a new breakthrough in C(sp³)−H bond oxidative coupling

Academician Zhou Qilin and Professor Xiao Lijun's team from Nankai University, in collaboration with Researcher Xue Xiaosong from the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, published a major research breakthrough in the international chemistry journal *Journal of the American Chemical Society* (JACS, IF=16.383). They developed a brand-new cationic copper catalysis strategy that achieves highly enantioselective oxidative coupling of allylic/propargylic C(sp³)−H bonds with carboxylic acids. In this study, the team used Advion Interchim Scientific’s expression CMS-L mass spectrometer to carry out the relevant detection and analysis, providing precise technical support for the rapid identification and verification of reaction products, helping this achievement in organic synthesis successfully come to fruition!

Breaking decades of limitations in organic synthesis

Direct enantioselective functionalization of C (sp³)−H bonds is one of the ultimate goals in organic synthesis. In particular, building C−O bonds through C (sp³)−H oxidation is a key route to synthesizing chiral esters and chiral alcohols, and these products are widely found in natural products, pharmaceuticals, and fine chemicals.

But for a long time, this field has faced many bottlenecks: traditional methods rely on peroxides as the oxygen source, substrates are mostly limited to cyclic alkenes, acyclic alkenes are less reactive, and over-oxidation often leads to ketone by-products, which seriously restricts practical applications.

Zhou Qilin's team broke through all these limitations this time:

✅ Abandon peroxides and use regular carboxylic acids as the oxygen source, greatly improving the practicality of the reaction;

✅ For the first time, the substrates have been extended to include open-chain alkenes and alkynes, significantly broadening the scope of the reaction.

✅ Under mild conditions (blue light irradiation, 0°C–10°C), we can achieve high yields (up to 82%) and high enantioselectivity (er up to 99:1), while also precisely controlling site selectivity and avoiding over-oxidation.

Broad application prospects, empowering pharmaceuticals and fine chemicals

This new method is not only important in the field of basic organic synthesis, but also shows great practical value.

✅ You can directly start from readily available alkenes and alkynes to synthesize various chiral allyl esters and propargyl esters in one step, greatly simplifying the synthesis steps of chiral oxygen-containing compounds;

✅ Successfully applied to drug molecules like ibuprofen and naproxen, as well as natural products like ursolic acid and zearalenone, achieving highly stereoselective modifications and providing new ways for drug development and natural product transformation.

✅ The reaction conditions are mild and it works with a wide range of substrates, making it promising for industrial applications and helping to upgrade green synthesis in fine chemicals and pharmaceuticals.。

Hardcore technology support, the expression CMS-L mass spectrometer helps all the way

Behind this achievement, precise analytical and detection techniques played a key role. The team used the AIS expression CMS-L mass spectrometer throughout the entire process of reaction optimization, substrate expansion, and product verification, relying on its core advantages to support their research.

To clarify the reaction mechanism, the research team successfully synthesized and characterized the key intermediates L3Cu(O'Bu)BArF (Int-I) and L3Cu(OBz)BArF (Int-II). They used the Advion expression CMS-L mass spectrometer (ESI source) to characterize these intermediates by mass spectrometry:

Positive ion mode: detected [M]⁺ = 471.3177 (calculated 471.0800);

Negative ion mode: detected [BArF]⁻ = 863.2059 (calculated value 863.0654).

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It's worth mentioning that traditional high-resolution mass spectrometry, due to its harsh ionization methods, causes fragmentation and fails to detect these intermediates. In contrast, expression CMS-L, with its mild ionization conditions and flexible tuning capabilities, successfully captured these 'fragile' key signals, becoming a 'game-changer' for mechanism research. It provides direct evidence for the intermediates in the reaction and strongly supports the proposed reaction mechanism.

Not just a testing tool, but also a research 'navigator'

In complex systems of asymmetric synthesis, the expression CMS-L mass spectrometer is like a chemist's 'third eye':

✅Monitor the reaction process in real time, moving from 'post-analysis' to 'real-time guidance,' adjusting reaction conditions whenever needed, and no longer wasting reagents and time.
✅Rapid qualitative analysis, the analysis time has been shortened from the traditional 30 minutes to 2 minutes;
✅ High sensitivity and resolution, accurately detecting trace products;
✅ Portable and efficient, highly compatible, covering all kinds of substrates and products.

From quickly screening products during reaction condition optimization, to verifying results after expanding the substrate scope, and then to accurately characterizing chiral ester products, the AIS expression CMS-L mass spectrometer, with its stable and precise performance, has become an important analytical tool for the team to explore reaction patterns and validate research findings, helping the research move forward efficiently.

“The expression CMS-L mass spectrometer frees us from the tedious purification-detection cycle. Now, we can check the progress of the reactions in the three reaction bottles while sipping coffee.”

—— Team member :Dr. Liu

Exploring new frontiers in research together

Zhou Qilin's team has long been dedicated to research on chiral catalysis and C−H bond functionalization. This latest achievement opens up a whole new direction for the asymmetric oxidation functionalization of C (sp³)−H bonds, once again highlighting the leading international position of Chinese chemists in this field. At the same time, it also proves the excellent performance of the expression CMS-L mass spectrometer. In the future, Advion Interchim Scientific will continue to support more research teams with high-quality instruments and technical services, helping more cutting-edge research outcomes emerge and promoting innovation in chemistry, medicine, and other fields!

（ Note: The research results mentioned in this article are cited from: J. Am. Chem. Soc. 2025, 147, 627−635, authors: Xian-Ming Liu et al., corresponding authors: Qilin Zhou, Lijun Xiao, Xiaosong Xue ）

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