Harry Stefan Andrew, Xiang Michael Richard, Holt Eric, Zhu Andrea, Ghorbani Fereshte, Patel Dhaval, Lectka Thomas
Department of Chemistry, Johns Hopkins University 3400 N. Charles St. Baltimore MD 21218 USA
Chem Sci. 2022 May 30;13(23):7007-7013. doi: 10.1039/d2sc01907h. eCollection 2022 Jun 15.
We report a photochemically induced, hydroxy-directed fluorination that addresses the prevailing challenge of high diastereoselectivity in this burgeoning field. Numerous simple and complex motifs showcase a spectrum of regio- and stereochemical outcomes based on the configuration of the hydroxy group. Notable examples include a long-sought switch in the selectivity of the refractory sclareolide core, an override of benzylic fluorination, and a rare case of 3,3'-difluorination. Furthermore, calculations illuminate a low barrier transition state for fluorination, supporting our notion that alcohols are engaged in coordinated reagent direction. A hydrogen bonding interaction between the innate hydroxy directing group and fluorine is also highlighted for several substrates with F-H HOESY experiments, calculations, and more.
我们报道了一种光化学诱导的、羟基导向的氟化反应，该反应解决了这个新兴领域中高非对映选择性这一普遍存在的挑战。基于羟基的构型，众多简单和复杂的结构单元展现出一系列区域和立体化学结果。显著的例子包括久未实现的难反应的香紫苏内酯核心选择性的转变、苄基氟化反应的优先选择以及罕见的3,3'-二氟化情况。此外，计算结果揭示了氟化反应的低势垒过渡态，支持了我们关于醇参与协同试剂导向的观点。通过F-H HOESY实验、计算等方法，还突出了几种底物中固有羟基导向基团与氟之间的氢键相互作用。
