The Development Of Non-Noble Metal Mediated Deuteration Strategies For Organic Compounds

Deuterium is a stable isotope of hydrogen and is widely used in drug discovery and material science to improve the metabolic stability of drugs or to extend the lifetime of materials because C-D bonds are more stable than C-H bonds.Currently,the commonly used deuterium systems often use expensive catalysts or deuterium reagents,and their high costs limit the application of deuterium compounds.To address this problem,in this paper,the existing deuterium substitution method is modified to reduce the cost of the reaction system by using non-noble metal reductants and catalysts.In the first part,a deutero-dehalogenation reaction using aluminum foil as the reducing agent and D2O as the deuterium source was achieved through the continuous destructive effect of mechanical forces on the metal surface.The deuteration process of deiodination,debromination,dechlorination and even defluorosulfate is achieved by using mechanochemistry to overcome the problem of deuterium evolution reaction in the conventional metalD2O system.Through an in-depth investigation of the reaction mechanism,it was found that the deutero-dehalogenation reaction in the mill ball may be completed through the direct participation of Al-D intermediate in the transmetallation pathway,which is significantly different from the conventional deutero-dehalogenation reaction mechanism.In the second part,the construction of a nickel-catalyzed amide β-site selective H/D exchange reaction system was realized.Based on the conclusion that the C-H activation process is reversible in the Ni-catalyzed C-H activation functionalization reported in the literature,two reaction systems,C(sp2)-H/D exchange and C(sp3)-H/D exchange,were constructed by studying different solvent systems and organic ligands.The extension of C-H activation functionalization to H/D exchange reaction was realized,which provides a feasible way to develop other non-noble metal-catalyzed H/D exchange reactions.