Orsi Douglas L, Yadav M Ramu, Altman Ryan A
The University of Kansas, Department of Medicinal Chemistry, Lawrence, KS 66045.
Tetrahedron. 2019 Aug 9;75(32):4325-4336. doi: 10.1016/j.tet.2019.04.016. Epub 2019 Apr 9.
-difluoroalkenes are an easily accessed fluorinated functional group, and a useful intermediate for elaborating into more complex fluorinated compounds. Currently, most functionalization reactions of -difluoroalkenes, with or without a transition metal-based catalyst system, involve the addition or removal of a fluorine atom to generate trifluorinated or monofluorinated products, respectively. In contrast, we present a complementary "fluorine-retentive" reaction that exploits an organocatalytic strategy to add phenols across -difluoroalkenes to deliver β,β-difluorophenethyl arylethers. The products are produced in good to moderate yields and selectivities, thus providing a range of compounds that are underrepresented in the synthetic and medicinal chemistry literature.
二氟烯烃是一种易于获得的氟化官能团,也是用于合成更复杂氟化化合物的有用中间体。目前,无论有无过渡金属催化剂体系,大多数二氟烯烃的官能化反应都涉及添加或去除一个氟原子,分别生成三氟代或单氟代产物。相比之下,我们提出了一种互补的“氟保留”反应,该反应利用有机催化策略,使酚类化合物加成到二氟烯烃上,生成β,β-二氟苯乙基芳基醚。产物的产率和选择性良好至中等,从而提供了一系列在合成化学和药物化学文献中未得到充分研究的化合物。