Site-selective C-H Functionalization Tuned By Auxiliary Groups

Transition metal-catalyzed functionalization of C-H bonds provides a direct,economical and efficient strategy for the construction of C-C bonds and C-Heteroatomic bonds.However,C-H bond is ubiquitous in organic compounds,and how to activate C-H bond efficiently and accurately has become a hot spot and difficult point in recent years.In particular,it is still very challenging to develop remote and site-selective C-H functionalization.In this paper,we mainly studied the functionalization of the remote C-H bond tuned by the directing group,and realized the meta or para C-H bonds site selective fluoroalkylation.This paper mainly includes the following four aspects:1)The selective difluoromethylation of meta or para C-H bonds of different aromatic compounds is realized by regulating the electricity of the coordination center of the directing group.The experimental results show that the difluoromethyl group can be selectively introduced on meta or para position based on the coordination of the directing group.And the successful realization of introducing difluoromethyl group to multiple drugs,so that our work has potential application value.2)The direct polyfluoroalkylation of aniline to C-H bond was realized by using readily available Mo(CO)6 as a catalyst.Mechanism experiments and theoretical calculations show that the formation of quaternary metallization intermediates by Mo(CO)6 and amide leads to the electrical change of aromatic rings,while the ligand positional hindrance effect leads to the/para-selective fluoroalkylation reaction and the realization of polyfluoroalkylation modification of drug molecules or their precursors3)A strategy was developed to activate the meta C-H bond by hydrogen bond guidance.N-acetyl glycine and hydroxyl groups in benzyl alcohol interact with each other through hydrogen bond to form a remote directing mechanism in the reaction system and realize palladium-catalyzed meta C-H alkenylation.The mechanism experiment and hydrogen bond experiment support the guidance mechanism of hydrogen-bond.4)A cheap pyrazole directing group was developed to realize the selective monoarylation of Rhodium-catalyzed alkyl substrate,and the Rhodium-catalyzed C-H arylation of alkyl secondary carbon for the first time.In addition,the directing group is easy to be excised and can be recovered for reuse,indicating that the pyrazole-assisted C-H bond activation has a potential application prospect.