Acid Switchable Reaction of CF3‑Ynones with Hydroxylamine To Form Selectively 3- and 5‑CF3‑Isoxazoles

Efficient regioselective one-pot approaches toward 5- and 3-CF3-isoxazoles were elaborated using reaction of hydroxylamine and its hydrochloride in ethanol. The reaction direction is easily switched by the acidity of the reaction media. In acidic conditions 3-CF3-isoxazoles are formed while 5-CF3-isoxazoles can be synthesized in basic media. High (up to 99%) yields, mild conditions, and simplicity of the reaction protocol are the advantages of the proposed methods. The reaction mechanism and regioselectivity were explained by DFT calculations.

以羟胺及其盐酸盐在乙醇中的反应为基础，本研究开发了针对5-三氟甲基异恶唑与3-三氟甲基异恶唑（5- and 3-CF3-isoxazoles）的高效区域选择性一锅法合成策略。反应方向可通过反应介质的酸度轻松调控：在酸性条件下生成3-三氟甲基异恶唑，而在碱性介质中则可合成5-三氟甲基异恶唑。所提出的合成方法具备收率高（最高可达99%）、反应条件温和以及操作流程简便等优势。本研究通过密度泛函理论（DFT）计算阐明了该反应的机理与区域选择性成因。