From H to F: Strategies in Selective sp3 C-H Fluorination

Catalysis;Fluorine;Methodology;Direct;Chemistry

Bloom, Steven PatrickPosner, Gary H. ;

Johns Hopkins University

关键词: Catalysis;    Fluorine;    Methodology;    Direct;    Chemistry;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/37992/BLOOM-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

The replacement of a single hydrogen atom by fluorine can impart a unique set of chemical and physical properties onto organic molecules, oftentimes modifying their reactivity.In many instances, fluorination improves the metabolic stability of pharmaceuticals, amplifies the electronic properties of polymers, and heightens the efficiency of industrial solvents and surfactants.Despite these and others, fluorination methods have endeavored to become commonplace, a fact consistent with the lack of synthetically mild sources of atomic fluorine.Until recently, fluorination strategies have been predicated upon the use of harsh, unselective, and often destructive sources of fluorine, such as fluorine gas and explosive hypofluorites, limiting their synthetic utility.Over the last 20 years, the advent of bench-top stable N-F reagents have incurred a renaissance in the discovery of regio- and chemoselective methods for the direct incorporation of fluorine atoms into organic molecules.In this Dissertation, the applications of one such N-F compound, 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) is highlighted as a practical reagent for the monofluorination of unactivated sp3 C-H bonds of aliphatic, benzylic, and allylic containing compounds in conjunction with earth-abundant, inexpensive transition metals and commercially available photocatalysts.The use of Selectfluor in the α,α-difluorination of acid chloride derivatives and photocatalyzed ring opening-β-fluorination of cyclopropanols is likewise discussed.Mechanistic evidence suggests the involvement of putative carbon-centered radicals (or radical ions) during fluorination with Selectfluor acting as a versatile fluorine atom transfer reagent.