Removable Directing Group Assisted Selective C-H Bond Fluorination

As the most common and basic chemical bond and structural unit in nature,carbon-hydrogen bonds are widely existed among various natural and synthetic organic compounds.The direct cleavage of inert C-H bond to construct new C-C or C-X bonds at a specific site presents an ideal synthetic protocol in organic chemistry,which could avoid the use of prefunctionalized substrates.Transition metal-catalyzed C-H bond activation strategy has become a primary method to build a C-C or C-X bond during the past decade,in which the removable directing group assisted C-H bond functionalization would dramatically extened the substrate scope and improve the application prospect of C-H bond activation protocols.In this dissertation,two examples of palladium-catalyzed,removable directing group assisted selective C-H bond fluorination of fundamental phenol and aromatic alcohol substrates were developed and described as follows:(1)Briefly explained the concept of directing group,C-H bond activation and fluorination.Recent advance in fluorination,especially in the transition metal-catalyzed C-H bond fluorination were extensively reviewed.(2)First example of ortho C-H bond fluorination of phenol derivatives directed by a 2-pyridyloxy group was reported,which featured in good yield and selectivity(up to 90%).Uesful substituted 2-fluorinated phenols were delivered via the removal of the directing group.In addition,late-stage and selective C-H bond fluorination of bio-active 2-phenoxyl nicotinate derivatives were also feasible under the present strategy,which may pave the way for the synthesis of fluorinated medicines and pesticides.(3)First example of ortho C-H bond fluorination of aromatic alcohol derivatives directed by exo-acetone oxime ether group was reported.The present protocol featured in good selectivity(up to 90%)and broad substrate scope via the formation of a six-or seven-membered exo-acetone oxime ether palladacycle intermediate.Uesful substituted 2-fluorinated aromatic alcohols could be obtained after removing the directing group.(4)Typical experiment sections as well as the characterization of the products were displayed.(5)Summary and outlook of the dissertation.