The Development Of N-Methoxyamide As An Effective Aminating Reagent

The construction of transition metal-catalyzed carbon-nitrogen(C-N)bonds has always been a hot and difficult point in organic chemistry.Building carbon-nitrogen(C-N)bonds from carbon-hydrogen bonds is the most direct,economical,efficient and green way.In recent years,transition metal-catalyzed carbon-hydrogen bond functionalization reactions have developed vigorously,making this type of synthetic methods play an increasingly important role in organic synthetic chemistry.However,how to develop a new type of highly efficient,cheap and readily available amination reagent and apply the amination reaction to the modification of biologically active molecules is still a problem that needs to be solved in organic synthesis methodologyIn this paper,N-methoxyamide was used as a new amination reagent.Transition metal catalyzed amidation of C(sp2)-H bond was reported.It was successfully applied to the later stage of direct modification of drug molecules.It has a wide application prospect in organic synthesis and exploration of new drug molecules.The main contents of this paper are as followsFirst of all,the mechanism of amidation of aromatic compounds and various amination reagents were summarized,and the reaction characteristics,advantages and disadvantages,and research significance were summarized.Secondly,for the first time,N-methoxyamide was used as amination reagent to study the transition metal catalyzed C-H bond amidation of aromatics.A kind of catalytic system with[Cp*IrCl2]2 as catalyst and AgSbF6 as additive was developed to realize the ortho amidation of 2-arylpyridine compounds.The reaction is suitable for a wide range of substrates,with strong functional group tolerance,and can obtain amidation products in medium to good yields,which has a broad application prospect.Finally,we first convert the bioactive carboxylic acid compounds,such as undecanone carbonic acid,PTC(124),rofluorostat intermediate,vitamin E,carboxy groups with adapalene,gabapentin and pregabalin.into N-methoxyamide.which is an effective amination reagent.Then,with the help of the rhodium catalytic system developed by us,the ortho C-H bond amidation reaction with N-methoxyamide as the amine source was used to connect it with well-known drugs,such as celecoxib and purine nucleoside,and a new complex molecule was constructed.This strategy may promote the discovery of new drug molecules and has important synthetic significance.