Palladium-catalyzed Amine Carbonylation Of Enol Silyl Ethers

Amide bond is one of the most common chemical bonds in nature,widely found in small organic molecules,natural products and drug molecules.Traditional amide synthesis methods are mainly achieved by the condensation of amines and carboxylic acids and their derivatives under the action of coupling reagents.However,these methods have problems such as generating a large amount of waste during the reaction.In recent years,transition metal-catalyzed C–H bond amine carbonylation has provided a gentle way for efficient construction of amide compounds.Organic azides have excellent reactivity and are widely used in the fields of chemistry and materials science.The synthesis of organic azide usually uses sodium azide as the nitrogen source reagent,but the use of sodium azide has some safety hazards,so it is of great significance to find a suitable reagent to replace sodium azide.In response to the above problems,azidotrimethylsilane is a commercially available nitrogen source reagent,which has important applications in the synthesis of nitrogen-containing compounds.This thesis mainly starts from the transition metal-catalyzed C–H bond amine carbonylation reaction to construct amide compounds.In this process,the efficient and green synthesis method of organic azides is first studied,and the organic azide compounds are used to achieve Pd-catalyzed The amidation reaction of enol silyl ether constructs?-ketoamide compounds.The main research results are as follows:1.The commonly used sulfonyl chloride is used as the reaction raw material to realize the direct and efficient method of synthesizing sulfonyl azide by the action of alkali.The reaction uses trimethyl silicon azide as the nitrogen source reagent,which not only obtains organic azide efficiently,but also improves the safety factor of the reaction operation.This method is simple to operate and can be applied to the gramlevel reaction preparation of organic azides.The reaction mechanism shows that at the beginning of the reaction,alkali can simultaneously activate sulfonyl chloride and trimethyl silicide.2.Using silyl enol ether with higher thermal stability as the raw material for the reaction,the palladium-catalyzed C-H bond amine carbonylation reaction was realized.The reaction uses carbon monoxide as the carbonyl source and organic azide as the nitrogen source to synthesize a series of amide compounds through the in-situ generation of isocyanate intermediates and the reaction of enol silyl ethers.The reaction has the advantages of no ligands,no oxidants,no additives and alkalis,mild conditions,simple raw materials and so on.