Chemistry Department, University of British Columbia , 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
J Am Chem Soc. 2012 Mar 7;134(9):4026-9. doi: 10.1021/ja211679v. Epub 2012 Feb 22.
The development of new synthetic technologies for the selective fluorination of organic compounds has increased with the escalating importance of fluorine-containing pharmaceuticals. Traditional methods potentially applicable to drug synthesis rely on the use of ionic forms of fluorine (F(-) or F(+)). Radical methods, while potentially attractive as a complementary approach, are hindered by a paucity of safe sources of atomic fluorine (F(•)). A new approach to alkyl fluorination has been developed that utilizes the reagent N-fluorobenzenesulfonimide as a fluorine transfer agent to alkyl radicals. This approach is successful for a broad range of alkyl radicals, including primary, secondary, tertiary, benzylic, and heteroatom-stabilized radicals. Furthermore, calculations reveal that fluorine-containing ionic reagents are likely candidates for further expansion of this approach to polar reaction media. The use of these reagents in alkyl radical fluorination has the potential to enable powerful new transformations that otherwise would take multiple synthetic steps.
随着含氟药物的重要性不断提高，用于有机化合物选择性氟化的新型合成技术得到了发展。传统的、可能适用于药物合成的方法依赖于氟离子（F(-) 或 F(+))的使用。尽管自由基方法作为一种互补方法具有吸引力，但由于缺乏安全的原子氟源（F(•)）而受到阻碍。已经开发出一种新的烷基氟化方法，该方法利用试剂 N-氟代苯磺酰亚胺作为氟转移试剂向烷基自由基转移氟。这种方法适用于广泛的烷基自由基，包括伯、仲、叔、苄基和杂原子稳定的自由基。此外，计算表明，含氟离子型试剂可能是进一步将该方法扩展到极性反应介质的候选试剂。在烷基自由基氟化中使用这些试剂有可能实现强大的新转化，否则这些转化需要多个合成步骤。
