Synthetic Methodology Research Of Indolizine Derivatives

Heterocyclic compounds are widespread in nature. Many important bioactive compounds are heterocyclic compounds, such as alkaloids, hormones, antibiotics and so on. The researches on synthetic methodology and biological activities of heterocyclic compounds have been wide concerned by chemists and biologists. As one of the most important heterocyclic compounds, nitrogen-containing heterocyclic compound which is common in natural products have potential biological activity. Indolizine which is indole's isomer is one of most important 10πelectron aromatic heterocyclic compounds.The application of organocatalysts in organic synthesis has been developed in the last decade. Compared with organometallic catalysts and biocatalysts, organocatalysts are usually more stable, more environmentally friendly, more readily available, less expensive and they can be applied under hydrous or aerobic conditions; and they can efficiently catalyze a kind of one-pot reactions such as cascade reaction, multi-component reaction. Tertiary amine is easy to form iminium salts and the activity of connected methylene is greatly enhanced, and it was easily removed, so it was used as an effective catalyst in varieties of organic synthesis.First, a series of novel indolizine derivatives have been obtained through pyridineα-bromoacetophenone salt and terminal alkyne or diyne as substrate in which we introduced alkynyl in indolizine which brings possible options of further modification of indolizine. And it also greatly broadened the synthesis method which only used DMAD and its derivatives as the substrate.Then, we introduced aldehyde in indolizine through Vilsmeier reaction. The corresponding 1, 3-dicarbaldehyde indolizine can react with 2-aminophenol at room temperature and obtained imine. In the presence of tertiary amine the obtained imine reacted with bromoacetophenone and we obtained a series of novel indolizine derivatives substituted by benzoxazine.