Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, 610052, China.
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, 610041, China.
Angew Chem Int Ed Engl. 2020 Jan 27;59(5):1863-1870. doi: 10.1002/anie.201912450. Epub 2019 Dec 5.
Fluorinated ketones are widely prevalent in numerous biologically interesting molecules, and the development of novel transformations to access these structures is an important task in organic synthesis. Herein, we report the multicomponent radical acylfluoroalkylation of a variety of olefins in the presence of various commercially available aromatic aldehydes and fluoroalkyl reagents through N-heterocyclic carbene organocatalysis. With this protocol, over 120 examples of functionalized ketones with diverse fluorine substituents have been synthesized in up to 99 % yield with complete regioselectivity. The generality of this catalytic strategy was further highlighted by its successful application in the late-stage functionalization of pharmaceutical skeletons. Excellent diastereoselectivity could be achieved in the reactions forging multiple stereocenters. In addition, preliminary results have been achieved on the catalytic asymmetric variant of the olefin difunctionalization process.
氟代酮广泛存在于许多具有生物学意义的分子中，因此开发新型转化方法来构建这些结构是有机合成中的一项重要任务。在此，我们通过 N-杂环卡宾有机催化，报告了在各种商业上可获得的芳醛和氟烷基试剂存在下，多种烯烃的多组分自由基酰基氟烷基化反应。通过该方案，可以高收率（高达 99%）和完全区域选择性合成超过 120 个具有各种氟取代基的官能化酮的例子。该催化策略的通用性通过其在药物骨架的后期官能化中的成功应用得到了进一步强调。在形成多个立体中心的反应中可以实现优异的非对映选择性。此外，在烯烃双官能化过程的催化不对称变体中也取得了初步结果。
