Studies On The Synthesis Of Several Heterocyclic Compounds

Diversity-oriented synthesis (DOS) has enormous implications for the synthesis and discovery of small molecules with desired properties for high-throughput screening (HTS) in the drug discovery process. Tandem reaction plays a decisive role acting as the strategy with atom economy and high efficiency in the diversity-oriented synthesis. This thesis focuses on the generation of some privileged scaffolds (chromene, benzo[f][1,2]thiazepine dioxide and 4-halo isoquinoline N-oxide) which exhibit remarkable biological activities through tandem reactions.In the first place, the novel and efficient routes for the preparation of chromenes and benzo[f][1,2]thiazepine dioxides via a palladium catalyzed tandem reaction of 2-alkynylvinylbromide were discovered. During the reaction process, the transformation proceeds through a double insertion of triple bonds in the presence of a palladium catalyst forming four new bonds and two new rings. High efficiency with good functional group tolerance could easily to be observed in the scope exploration as well.Then we investigated an efficient method for the synthesis of diverse isoquinoline N-oxides in water. The hypobromite or hypoiodite is generated in situ under mild conditions. We have also shown that the cyclization of 2-alkynylbenzaldoximes and the palladium-catalyzed Suzuki cross coupling process using arylboronic acids could be performed in one pot, leading to functionalized isoquinoline N-oxides in good yields. The combination of oxone-NaBr/NaI instead of halogen simplifies the operation and reduces the toxicity to the operators and the environment. It is possible to achieve diversity of isoquinoline N-oxides efficiently through this green route.