Studies On The Synthesis Of Heterocyclic Compounds Catalyzed By Iron Salt

The new methods to synthesize 3-quinolinecarboxylic ester,4H-chromene, chromane and 2-pyrroline derivatives catalyzed by the inexpensive and readily available iron salt are described in this thesis. Based on the reported methods, we present novel protocols to synthesize these heterocyclic compounds. In this thesis, three parts are included. The first part is about the recent development of iron salts as catalysts in organic chemistry and its application; the second part focuses on the the synthesis of heterocyclic compounds catalyzed by iron salt; the last section briefly states the synthesis of several anti-HIV leading compounds.1. Iron-catalyzed synthesis of heterocyclic compoundsBased on the benzylic reaction of styrene and acetylacetone, we achieve to synthesize the following types of heterocyclic compounds.1) Using (2-aminophenyl)methanol as the benzylic reagent reacting with acetylacetone, we get 3-quinolinecarboxylic ester. In this process, the benzylic reaction is the first step; then the cyclization of amine and carbonyl happen and form a 1,4-dihydro-3-quinolinecarboxylic ester. The 1,4-dihydro-3-quinolinecarboxylic ester is not a stable skeleton and can be oxidated to 3-quinolinecarboxylic ester under oxidizing condition. The protocol reported here is a great complement to the traditional Friedlander method for the quinoline synthesis and exhibit an important application value.2) Based on the synthesis of 3-quinolinecarboxylic ester, we extend (2-aminophenyl)methanol to 2-(hydroxymethyl)phenol and achieve to synthesize the 4H-chromene skeleton. The possible passway is the benzylic step followed by the cyclization of hydroxy and carbonyl group. This method provides a new idea for the synthetic methodology of 4H-chromene.3) Owning to the participation of the ortho-phenol hydroxyl group, we discover a novel palladium-catalyzed isomerization of alkene. The mechanism reveal that sequential 1,3-hydride alkyl to palladium migration is involved. Both of deuterium labeling experiment and interval NMR experiment prove this process. Also, this developed isomerization is very useful in the preparation of benzofuran derivatives.4) Based on the synthesis of 3-quinolinecarboxylic ester and 4H-chromene, using allylsilane as the nucleophilic reagent, we get chromane product with silylmethyl substituent at the 2-position. In this process, a significant (3-effect of silicon is involved.5) Extending the nucleophilic reagent to aziridine, under the iron salt catalyst, the in situ zwitterion could react with alkyne to generate 2-pyrroline product. Additional experiments reveal that aryl-substituted alkenyl cation is the key intermediate and substrates which cannot form this aryl-substituted alkenyl cation exhibit no reactivity. Besides, we achieve a novel and effective method to synthesize y-amino ketone in one-pot protocol.2. Synthesis of anti-HIV leading compoundsIn my spare time of studying on the synthesis of heterocyclic compounds catalyzed by iron salt, I carry out a second program about synthesizing of anti-HIV leading compounds. The key structure of these compounds is polyamine. The difficulty of the synthesis is the selective functionalization of polyamine.