Br(?)nsted Acid Or Lewis Acid-Catalyzed Cyclization Of Enaminone Compounds

Cyclic structures occur widely in many natural products and pharmaceuticals. Especially the heterocyclic compounds display a wide range of bioactivities. They can also find a variety of applications in medicine, agricultural chemicals and biological chemistry. Therefore, the development of efficient and direct approaches for cyclization reactions is very important. Enaminones are important synthetic intermediates in organic chemisrty. It combines the ambident nucleophilicity of enamines with the ambident electrophilicity of enones due to their unique struture. As a cosequence, they are widely used in the synthesis of cyclic compounds. This thesis focused on the development of novel synthetic methodologies for cyclic compounds starting from enaminone derivatives. It has been found that heterocycles such as dihydropyridines, furans could be prepared from enaminones in good to exellent yields with high selectivity. In the mean time, the iodine mediated cyclization of2-alkynylbenzyl alcohols to2,3-disubstituted indenones was also developed. These results are quite different from the reported iodocyclization reactions. The thesis includes the following four parts.1. Acid-catalyzed approach to the synthesis of functional1,4-dihydropyridines from the reactions of readily available enaminones with aldehydes was established. This methodology was realized by a cascade reaction involving first formation of divinyl methanes followed by cyclization. And the1,4-dihydropyridines were obtained in48%-90%yields. The structure was fully confirmed by X-ray crystallographic analysis.2. An efficient procedure for the construction of1,4-dihydropyridines without substituent at the C-4position from the reaction of enaminones and dimethyl sulfoxide has been developed. Formaldehyde and methanethiol may be generated from Dimethylsulfoxide in acidic condition. A regioselective synthesis of1,4-dihydropyridines or3-carbonyl quinoline derivatives was realized by changing the reaction conditions. 3. Palladium/copper-catalyzed approach to the synthesis of highly substituted3-formyl furans from the reactions of readily available a-bromoenaminones with terminal alkynes has been developed. This methodology was realized by the cascade reactions of Sonogashira coupling and the subsequent intramolecular cyclization. The yield of the3-formyl furans were from35%-83%.4.I2-mediated approach to the synthesis of disubstituted indenones from readily available2-alkynylbenzyl alcohols in the presence of H2O has been developed. This methodology was realized by the cascade reactions of neucleuophilic attack of H2O to the triple bond and the subsequent intramolecular cyclization with the carbocation.