Zisheng and Zhengzhao's work highlighted by Organic Process Research & Development

2026-09-24

Our paper "Carbonyl swapping converts cyclic ketones to saturated heterocycles" (Nature, 2026) has been highlighted in Organic Process Research & Development (read the highlight article here). Congratulations again to Zisheng, Zhengzhao, and co-authors!

“The Xu group at Peking University recently unveiled a method offering process chemists a new disconnection, in essence replacing a carbonyl group in a cyclic ketone with a heteroatom such as nitrogen, oxygen, sulfur, selenium, or tellurium (Nature, DOI: 10.1038/s41586-026-10508-5). The transformation proceeded via a unique bis(aroylperoxy)ketal intermediate, which enabled the sequential cleavage of two carbon–carbon bonds adjacent to the carbonyl group. With iron(III) chloride as the catalyst and simple nucleophiles, the reaction generated dichloride intermediates that could be converted into diverse heterocycles in good yields. The method demonstrated broad substrate scope and functional-group tolerance, working efficiently with five-, six-, and seven-membered rings and complex natural-product and API-like derivatives. It also allowed late-stage modification of bioactive molecules, offering a new route to medicinally relevant scaffolds such as piperidines and morpholines. The process could be integrated with established ring-construction or ring-functionalization strategies, enabling rapid access to complex heterocycles from simple building blocks. An extension combined carbonyl replacement with C–H oxidation to achieve a formal methylene-to-heteroatom (CH2 to X) conversion, suggesting potential for future skeletal editing applications. This transformation was also demonstrated on a 2 g scale to highlight its potential for process development, even though the reported yields remain modest. Overall, the study presented a versatile and scalable platform for ring transmutation, expanding the toolkit for constructing and diversifying saturated heterocycles from simple ketone precursors."