Synthesis Of Butenolide And Butyrolactam Compounds By Carbonylation Reaction

Butenolide and butyrolactam compounds are the core skeletons of many natural products.They have diverse biological activities and are of great significance for the development of new drug molecules.Therefore,in the past few decades,the synthesis of butenolide and butyrolactam compounds has attracted great attention from chemists.There are various methods for the synthesis of butenolide and butyrolactam compounds,such as:intramolecular condensation reaction,redox reaction,elimination reaction,carbonylation reaction,etc.,which can be divided into traditional synthetic methods and carbonylation reaction.Among them,traditional synthetic methods have harsh requirements for substrates,redundant synthesis steps,and strict reaction conditions.The carbonylation synthetic method has obvious advantages.It directly introduces carbonyl groups and synthesizes corresponding butenolide and butyrolactam compounds.From simple carbonyl compounds to complex compounds with butenolide and butyrolactam structures,the carbonylation synthetic method is the most convenient and has high atom economy.In the carbonylation reaction,because carbon monoxide gas is highly toxic,colorless,odorless,and highly flammable,it is very harmful to the human body.Therefore,it is necessary to configure related equipment and safety monitoring systems when using carbon monoxide gas.The generation of green alternative carbonyl sources solves this problem.It not only reduces the risk factor of reaction operation,but also broadens the synthetic method of the product,and at the same time has the potential to explore new chemical products.This thesis is based on the substitution of carbonyl sources,palladium-catalyzed carbonylation of propargyl alcohols and propargyl amines to synthesize butenolides（butenolide and4-aroyl butenolide compounds）and butyrolactams（2-oxo-2,5-dihydropyrrole and 1,3-diaryl-1,5-dihydro-pyrrole-2-one compounds）.The specific content is as follows:1.Using TFBen（1,3,5-tricarboxylic acid phenol ester）as carbonyl source,palladium-catalyzed carbonylation reaction of propargyl alcohols to synthesize butenolides.This reaction directly constructs various substituted butenolides,And the mechanistic study proves that the phloroglucinol decomposed by TFBen can promote the formation of the product.2.Using Cr（CO）₆as carbonyl source,palladium-catalyzed double carbonylation reaction of propargyl alcohols and aryl triflates to synthesize 4-aroyl butenolides.This reaction realizes the one-step synthesis of the double carbonylation product,and obtains the core skeleton of a variety of drug molecules with high yields.3.Using TFBen as the carbonyl source,palladium-catalyzed carbonylation of propargyl amines to synthesize 2-oxo-2,5-dihydropyrrole compounds.This reaction has a wide range of substrate applicability.4.Using TFBen as the carbonyl source,palladium-catalyzed double carbonylation of propargyl amines and aryl halides to synthesize 1,3-diaryl-1,5-dihydropyrrole-2-one compounds.This reaction realizes the one-step synthesis of dihydropyrrolone compounds with mild conditions and good functional group compatibility.