近日，北京大学许言团队报道了羰基交换将环酮转化为饱和杂环。相关论文于2026年4月15日发表在《自然》杂志上。

饱和杂环是生物活性分子中的优势骨架。尽管已有多种从头合成路线可获得各类杂环化合物，但从统一且易得的碳环出发构建多样化的杂环，将为利用非常规前体合成具有挑战性的杂环结构提供一种策略性替代方案。

研究组报道了一种模块化方法，通过一种鲜有研究的双(芳甲酰过氧)缩酮中间体，将单一环酮经杂原子形式上的羰基置换转化为多种饱和杂环。通过电子导向的过氧键断裂，该中间体实现环酮的双重C–C键断裂，生成烷基二氯化物作为通用连接臂，进而利用简单亲核试剂模块化引入N、O、S、Se、Te原子。

该方法具有广泛的底物范围和官能团耐受性，既可加速目标分子的合成，又能实现生物活性分子的后期多样化修饰。通过“环构建–羰基置换”和“环官能化–羰基置换”策略，该方法的实用性进一步扩展：将经由成熟方法制备的环酮转化为难以获得的杂环，而针对这些杂环的类似合成方法仍不成熟。进一步地，通过将C–H氧化与羰基置换相结合，展示了概念验证性的形式“CH₂到杂原子”转化。

附：英文原文

Title: Carbonyl swapping converts cyclic ketones to saturated heterocycles

Author: Xue, Zisheng, Lou, Zhengzhao, Lou, Xiang, He, Peimiao, Wang, Jianbo, Xu, Yan

Issue&Volume: 2026-04-15

Abstract: Saturated heterocycles are privileged scaffolds in bioactive molecules.1 Despite the availability of numerous de novo routes to various heterocyclic compounds, accessing diverse heterocycles from a unified, readily available carbocycle would offer a strategic alternative for constructing challenging heterocyclic structures from unconventional precursors.2 Here we report a modular approach that transforms a single cyclic ketone into various saturated heterocycles through formal carbonyl replacement with heteroatoms, via a scarcely explored bis(aroylperoxy) ketal intermediate. Through electronically guided peroxy cleavage, this intermediate enables double C–C bond scission of cyclic ketones, generating alkyl dichlorides as versatile handles for modular N/O/S/Se/Te incorporation using simple nucleophiles. This method exhibits broad substrate scope and functional-group tolerance, enabling both accelerated target synthesis and late-stage diversification of bioactive molecules. Its utility is also extended through “ring construction–carbonyl replacement” and “ring functionalization–carbonyl replacement” strategies, whereby cyclic ketones prepared via well-established methods are converted into challenging-to-access heterocycles for which analogous methods remain underdeveloped. By combining C–H oxidation with carbonyl replacement, a proof-of-concept formal “CH2-to-heteroatom” conversion is further demonstrated.

DOI: 10.1038/s41586-026-10508-5

Source: https://www.nature.com/articles/s41586-026-10508-5