Study On Paal-Knorr Cyclization Catalyzed By Mg(?) And The Asymmetric Total Synthesis Of Natural Product Epicurcumenol

This thesis aims at the study on Paal-Knorr cyclization of substituted1,4-diketones with primary amines promoted by Lewis acidic MgI₂??OEt₂?_n and the asymmetric total synthesis of guaiane sesquiterpenes natural product epicurcumenol.This dissertation consists of two parts as following:In the first part,we reviewed the methodology for the synthesis of pyrrole and its derivatives,which is focused on the classic Paal-Knorr reaction.We investigated the Paal-Knorr reaction of substituted1,4-diketones with aromatic primary amines,aliphatic primary amines and chiral primary amines promoted by MgI₂??OEt₂?_n.We examined the effects of solvent,temperature and catalyst on the reaction.The experimental results showed that MgI₂??OEt₂?_n can efficiently catalyze Paal-Knorr reaction of 1,4-diketones with primary amines under solvent-free condition and afforded a series of N-substituted pyrrole compounds.As well,this catalysis system demonstrated the unique catalytic reactivity of MgI₂??OEt₂?_n in the chemoselective Paal-Knorr reaction of aromatic amines with 1,4-diketone:?1?aromatic amines are reactive substrates towards 2,5-hexanedione,when we use different aromatic amines with 2,5-hexanedione in cross reaction,MgI₂??OEt₂?_n show the high selectivity in steric effect of aromatic amines;?2?aromatic amines with electron-donating substituted?i.e.,o-or p-Me,-OMe?reacted much faster than aniline and electron-withdrawing substituted?i.e.,-NO₂,-Cl,-F?deactivated aromatic amines remarkably;?3?The experimental results also showed that Paal-Knorr reaction promoted by MgI₂??OEt₂?_n can retain the absolute configuration of substrates,which provide an efficient preparation of chiral pyrrole.This magnesium-catalyzed Paal-Knorr reaction is mild,efficient and operationally simple.In the second part,we briefly introduced the carbene carbonyl ylide cycloaddition cascade?CCCC?reaction and its application into the synthesis of natural products.According to the unique skeleton and important pharmacological activities of guaiane sesquiterpenoid,we have explored the total synthesis of natural product epicurcumenol.The key intermediate[5,7]oxatricyclic ketone was obtained through 15 steps starting from readily available 3-butyn-1-ol.The key steps of this synthetic strategy includs:introduction of chiral methyl group in?-position of carbonyl group by Evans asymmetric alkylation with high stereoselectivity;utilization of Normant's Grinard reagent into rapidly prolonging the carbon chain;diazomethane nucleophilic replacement to get the precursor compound;rhodium carbene carbonyl ylide cycloaddition cascade reaction to construct the key ring skeleton.Thus this project will be very helpful to the asymmetric total synthesis of epicurcumenol,which provides the constructive suggestion for the total synthesis of guaiane sesquiterpenoid natural products.