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

• 成果类型: Article
• 署名作者: Spennacchio, Mauro; Bernus, Miguel; Stanic, Jelena; Mazzarella, Daniele; Colella, Marco; Douglas, James J.; Boutureira, Omar; Noel, Timothy
• 署名单位: University of Amsterdam; Universita degli Studi di Bari Aldo Moro; Universitat Rovira i Virgili; University of Padua; AstraZeneca
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13054
• DOI: 10.1126/science.adq2954
• 发表日期: 2024-08-30
• 关键词: alcohols; dehydroxytrifluoromethylthiolation; chemistry; reagents; amines; ethers; esters; mild; side; salt

摘要

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 CF(3 )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.