Chem. SCI.: daihuixiong group of Shanghai Institute of medicine, Chinese Academy of Sciences first used oxime ester to realize selective C-H bond primary amination

Primary amines are important synthesis intermediates, and amino groups, as a kind of important pharmacodynamic groups, widely exist in drug molecules In recent years, the development of highly regioselective primary amination of C-H bonds is a hot research direction in the field of organic chemistry However, several cases of transition metal catalyzed primary amination of C-H bonds reported so far still have some limitations, such as poor substrate compatibility, poor regional selectivity, special primary amination reagents, large toxicity and narrow application range On June 13, 2018, chemical science, the authoritative comprehensive chemical Journal of the Royal Society of chemistry, published the scientific research results on C-H bond primary amination on the back cover The corresponding author of the paper is Dai Huixiong, researcher of Shanghai Pharmaceutical Institute, Chinese Academy of Sciences, and the co first author is Xu Linlin (co cultured) and Wang Xingwei, master's graduate student In 2014, Dai Huixiong's research group developed a new guiding group, oxazolidine amide guiding group, and successfully realized the amination (j.am Chem SOC 2014, 136, 3354), trifluoromethylation (angel Chem Int ed 2014, 53, 10439), Alkynylation (j.am Chem SOC 2014, 136, 11590), aromatization (org Lett 2014, 16, 5666), etc The strong bidentate coordination of oxazoline can overcome the adverse effect of heteroatoms in heterocycles on the selective activation of C-H bond, which enables the activation and functionalization of C-H bond to occur in the guiding group neighborhood with high selectivity These methods have been successfully applied to the late functional group site modification of telmisartan, an antihypertensive drug with multiple heterocycles (angel Chem Int ed 2017 , 56 , 5317 ）。 On the basis of previous work, for the first time, researchers have realized selective primary amination of aryl group and complex system containing multiple heterocycles by using safe and cheap oxime ester as primary amination reagent promoted by copper (chem.sci 2018, 9, As primary aminating agent and internal oxidant, oxime ester has two obvious advantages besides safety and cheapness: first, oxime ester has strong oxidation ability and can realize metal catalytic circulation without additional oxidant; second, the imine produced by reaction can obtain the target product under mild hydrolysis conditions, and the ketone produced can also be recovered almost equivalently This reaction breaks through the limitations of the previous C-H primary amination methods, realizes the selective primary amination modification and modification of the complex drug molecular structure, and provides a good idea for the construction of arylamino acids and aryl ammonia products Copper promoted aryl ortho amination (picture source: chem SCI.) the research work was supported by NSFC, youth innovation promotion association of Chinese Academy of Sciences, Pharmaceutical Innovation Research Institute of Chinese Academy of Sciences, Shanghai Municipal Committee of science and technology, and Shanghai Institute of pharmaceutical research of Chinese Academy of Sciences.