Photoredox-Catalyzed Hydrogen Isotope Exchange Reactions Of Amines

Deuterium-labeled pharmaceutical compounds are pivotal diagnostic tools in drug discovery research,providing vital information about the biological fate of drugs and drug metabolites.Therefore,the development of convenient and efficient methods for the synthesis of various deuterated compounds is of great interest.Direct hydrogen isotope exchange(HIE)at C-H bonds for deuterium enables the synthesis of labeled compounds in a single step.However,current catalytic systems have limitations such as harsh reaction conditions,narrow substrates ranges and single reaction sites.In this paper,the work focuses on the use of green,low-energy light-induced photoredox catalysis to study the HIE of C(sp3)-H in primary amines.This method can achieve good and excellent deuterium incorporations and corresponding deuterated a-primary amines.In this thesis,we will introduce it in two parts.The first part,we review the application and synthesis of deuterated compounds.The second part,in this thesis,we described a novel and direct hydrogen isotope exchange reaction of primary amines via visible-light-induced photoredox catalysis method.1-methyl-3-phenylpropylamine was used as a simple template.Then,through the investigation of the condition parameters such as deuterated reagents,photocatalysts,hydrogen transfer catalysts,solvents and base,we identified the optimal reaction conditions.The one-pot method is used to prepare deuterated amines with mild conditions,strong selectivity,and the purification steps of products are relatively simple.It only needs extraction without tedious chromatographic purification can be separated to get pure amide product.On this basis,we probed the substrate scope of this H/D exchange reaction of amine.Then,we found that most primary amines at a-positions for this reaction system.Finally,all the substrates can reach good and excellent deuterium incorporations,and their structures were characterized by 1H NMR and 21 NMR.