Exploring Base-Promoted Benzyl Deuteration

Deuterium-labeled compounds are one of the most commonly used compounds in isotope labeling research,and have very important applications in analytical chemistry,synthetic chemistry,biomedicine and other fields.Especially since the first deuterated drug was approved for marketing in 2017,research related to deuterated drugs has attracted the attention of many researchers,and the demand for deuterated compounds in various studies is also increasing.Therefore,how to synthesize deuterated compounds quickly and efficiently has become the focus of researchers.Ttraditional synthetic methods of deuterated compounds mainly include stepwise synthesis from small molecules containing deuterium,reduction of deuterated reagents,transition metal-catalyzed coupling,and hydrogen-deuterium exchange reaction.Considering the high efficiency and economy of the reaction,the hydrogen-deuterium exchange reaction promoted by acid-base without metal participation has attracted the attention of synthetic chemists.Our research group has been committed to the research of alkali-promoted chemical reactions,especially in the research of rBuOK as base reaction system,and has achieved many research results.After recognizing the application value of deuterium-labeled compounds,this article studied the alkali-promoted hydrogen-deuterium exchange reaction based on the previous work.By screening the reaction solvent,base,reaction temperature,time and other conditions,we determined the optimal conditions for the hydrogen-deuterium exchange system and conducted extensive research on its applicable substrates.The research results show that the reaction system can achieve selective deuteration of methyl groups in methyl aromatic compounds by using cheap bases(tBuOK and NaOH)in DMSO-d6 solvent,with high efficiency and a wide range of applications.