荷兰阿姆斯特丹大学Timothy Nol团队开发了一种制备和使用三氟甲基-杂原子阴离子的统一流程策略。相关研究成果于2024年8月30日发表在《科学》。

三氟甲基（CF₃）是药物和农用化学品开发中的关键物质，大大提高了所得化合物的功效和性能。然而，由于缺乏通用的合成方法和对定制试剂的依赖，将CF₃基团连接到硫、氧和氮等杂原子上带来了挑战。

该文中，研究人员提出了一个模块化的流动平台，简化了杂原子-CF₃基序的合成。该方法使用现成的有机前体，结合氟化铯作为主要氟源，促进按需快速产生N-三氟甲基（R）[NCF₃（R）]、SCF₃（三氟甲基硫）和OCF₃（三氟甲氧基）阴离子，而不依赖于全氟烷基前体试剂。

该策略提供了一种更环保的含三氟甲基（杂原子）分子的合成方法，通过流动技术促进了制造过程的可扩展性。

附：英文原文

Title: A unified flow strategy for the preparation and use of trifluoromethyl-heteroatom anions

Author: Mauro Spennacchio, Miguel Bernús, Jelena Stani, Daniele Mazzarella, Marco Colella, James J. Douglas, Omar Boutureira, Timothy Nol

Issue&Volume: 2024-08-30

Abstract: The trifluoromethyl group (CF3) is a key functionality in pharmaceutical and agrochemical development, greatly enhancing the efficacy and properties of resulting compounds. However, attaching the CF3 group to heteroatoms such as sulfur, oxygen, and nitrogen poses challenges because of the lack of general synthetic methods and reliance on bespoke reagents. Here, we present a modular flow platform that streamlines the synthesis of heteroatom-CF3 motifs. Our method uses readily available organic precursors in combination with cesium fluoride as the primary fluorine source, facilitating the rapid generation of N-trifluoromethyl(R) [NCF3(R)], SCF3 (trifluoromethylthio), and OCF3 (trifluoromethoxy) anions on demand without reliance on perfluoroalkyl precursor reagents. This strategy offers a more environmentally friendly synthesis of trifluoromethyl(heteroatom)–containing molecules, with the potential for scalability in manufacturing processes facilitated by flow technology.

DOI: adq2954

Source: https://www.science.org/doi/10.1126/science.adq2954