Synthetic Methodology Development Of Bis-1,3-Dicarbonyl Compounds And N,N-Disubstituted Enaminate Compounds

This thesis includes the following two parts:In the first part,a brief introduction is given to study of synthetic methods for the construction of bis-1,3-dicarbonyl compounds from different methylene synthons.While dichloromethane,as a special type of methylene synthon,can easily react with amine nucleophilic reagents to form reactive imine ions,leading to the construction of C-N bond.Inspired by this reaction pattern,a new strategy for the construction of methylene-bridged bis-1,3-dicarbonyl compounds has been developed using dichloromethane as the one-carbon source.Through the synergistic effect between dichloromethane and pyrrolidine under metal-free and oxidant-free conditions,bis-1,3-dicarbonyl compounds and their derivatives have been efficiently synthesized through redox-neutral reaction.The advantages of this protocol are mild reaction conditions and good functional group compatibility,providing the methylene bridged products in moderate to good yields.Meanwhile,the bis-1,3-dicarbonyl products can be further transformed into heterocyclic molecules with potentially biological activities such as polysubstituted pyridine and bipyrazole derivatives(Chapter 1).In the second part,an overview of the research progress on enaminones(esters)is presented.Since these molecules can serve as important structural motifs in various natural drug molecules and biologically active molecules,as well as important precursors for the preparation of chiral β-amino acid derivatives,they are of great value in scientific research and practical applications.The synthetic strategies for primary,secondary and tertiary enaminones(esters)are summarized accordingly.Meanwhile,combining with the research basis of our group in the synthesis and application of N,Ndisubstituted aminomalononitriles,we have successfully developed a copper-catalyzed reaction of N-aryl glycine esters with N,N-disubstituted aminoacrylonitriles assisted by chloranil,providing a novel strategy for the highly selective synthesis of N,Ndisubstituted Z-type enaminone esters.This type of enaminate compounds can be further transformed into 3-cyano-substituted indole derivatives,and the presence of cyano groups might facilitate the subsequent derivatizations(Chapter 2).