美国芝加哥大学Guangbin Dong团队通过顺序双碳-碳键激活实现羰基-硫交换。相关论文于2025年6月12日发表在《科学》杂志上。

在药物开发中，用硫原子取代骨架碳可以产生具有改进性能的生物活性化合物的类似物。目前，硫类似物几乎完全通过从头合成制备；现有的碳硫交换方法效率低下，涉及化学计量汞试剂。研究组报告了一种两步羰基到硫（CO-to-S）原子交换方法，该方法由合理设计的N′-烷基腙酰胺（NAHA）试剂实现，该试剂通过不同的机制促进前芳香族中间体的形成，从而实现酮底物的α-C-C键的均裂。 

Ts-S-Ts（Ts，对甲苯磺酰基）试剂通过中心硫连续捕获分子间和分子内烷基来介导这一过程。该方法显示了广泛的底物范围和优异的化学选择性，为从现成的酮中获得含硫支架提供了一条简化的途径。

附：英文原文

Title: Carbonyl-to-sulfur swap enabled by sequential double carbon-carbon bond activation

Author: Zining Zhang, Guangbin Dong

Issue&Volume: 2025-06-12

Abstract: In drug development, replacement of a skeletal carbon with a sulfur atom can result in analogs of bioactive compounds with improved properties. Currently, the sulfur analogs are almost exclusively prepared by de novo synthesis; the existing approach to swap carbon with sulfur is inefficient and involves stoichiometric mercury reagents. In this study, we report a two-step carbonyl-to-sulfur (CO-to-S) atom swap approach, enabled by a rationally designed N′-alkyl-hydrazonamide (NAHA) reagent that promotes forming pre-aromatic intermediates twice sequentially by different mechanisms, thereby achieving homolytic cleavage of both α-CC bonds of the ketone substrates. A Ts-S-Ts (Ts, p-toluenesulfonyl) reagent mediates this process through successive intermolecular and intramolecular alkyl radical trapping by the central sulfur. This method shows a broad substrate scope and excellent chemoselectivity, providing a streamlined route to sulfur-containing scaffolds from readily available ketones.

DOI: adx2723

Source: https://www.science.org/doi/10.1126/science.adx2723