Copper-Catalyzed One-Pot Synthesis Of α-Ketoamides

Amides,α-ketoamides and their derivatives are ubiquitous in natural products and drug molecules,are important components of many chemical products and modern drugs,and have a wide range of biological activities.As early as the end of the 20th century,α-ketoamides attracted the attention of the majority of medicinal chemists.Although scientists have proposed a variety of efficient synthesis methods,there are still complex substrates,the use of toxic reagents,cumbersome experimental steps,and reaction conditions,harsh,low yield and other issues.Therefore,the development of more efficient synthesis methods that conform to the concept of green and environmental protection is a hot research topic.In this paper,following the principles of green chemistry and economical application,the readily availableα-carbonyl diazonium compounds andα-aminocarbonyl compounds were finally selected as substrates,and reacted with nitrogen oxides compounds respectively,and two kinds of syntheticα-ketoamides were explored.method:（1）In the second chapter,we study the oxidative amidation reaction between diazonium compounds and nitrogen oxides.Various types ofα-ketoamide derivatives were successfully synthesized under nitrogen atmosphere using cuprous iodide as catalyst,potassium carbonate as base,α-carbonyl diazonium compound and 4-benzoic acid morpholine ester as substrates.The reaction conditions are mild,avoid the use of additional oxidants and additives,and have a wide range of substrates,and the nitrogen oxides in the reaction are both amine sources and oxidants.（2）The third chapter briefly describes the oxidative amidation ofα-aminocarbonyl compounds and nitrogen oxides.This is a one-pot method for synthesizingα-ketoamides with 4-benzoic acid morpholine ester andα-aminocarbonyl compound as substrate and cuprous chloride as catalyst.The method is easy to operate,has both the cleavage of C-N bonds and the formation of new C-N bonds in the reaction,no base is involved,the reaction temperature is low,and the substrates of the reaction are widely applicable.The nitrogen oxides in it play a dual role,solving the problem of requiring additional oxidants.Finally,the possible reaction mechanism was inferred by the exploration experiment,and the purified product was confirmed by ¹HNMR and ¹³CNMR nuclear magnetic properties to determine the structure of the product.In summary,the two synthetic routes proposed in this paper provide feasible ideas for solving the problems of cumbersome reaction steps,use of toxic reagents,addition of additional oxidants and additives,and low yields in traditional synthetic methods.At the same time,the synthesis methods ofα-ketoamides are also enriched,which lays a foundation for the further exploration ofα-ketoamides.