Selective C(sp3)−H and C(sp2)−H Fluorination of Alcohols Using Practical Auxiliaries

• Published in: Angewandte Chemie International Edition 2018-10, Vol.57 (43), p.14085-14089
• Main Authors: Mao, Yang‐Jie, Lou, Shao‐Jie, Hao, Hong‐Yan, Xu, Dan‐Qian
• Format: Article
• Language: English
• Subjects: Acetone; Alcohol; Alcohols; C−H activation; Fluorination; Fluorine; Hydrogen bonds; Organic chemistry; palladium; synthetic methods
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201808021

Selective introduction of fluorine into molecules by the cleavage of inert C−H bonds is of central academic and synthetic interest, yet remains challenging. Given the central role of alcohols in organic chemistry as the most ubiquitous building blocks, a versatile and selective C(sp3)−H and C(sp2)−H fluorination of simple alcohols, enabled by novel designed exo‐directing groups, is described. C(sp2)−H bond fluorination was achieved by using a simple acetone oxime as auxiliary, whereas a new, modular and easily accessible bidentate auxiliary was developed for the efficient and site‐selective fluorination of various primary methyl, methylene, and benzylic C(sp3)−H bonds. Fluorinated alcohols can readily be accessed by the removal of auxiliaries, and significantly expands the synthetic prospect of the present procedure. A versatile and selective C(sp3)−H and C(sp2)−H fluorination of simple alcohols, enabled by an exo‐directing group (DG) is described. C(sp2)−H bond fluorination was achieved by using simple acetone oxime as an auxiliary, whereas a new and modularly accessible bidentate auxiliary was developed for the efficient and site‐selective fluorination of C(sp3)−H bonds. The auxiliary is removable and demonstrates broad substrate scope and excellent selectivity.