The Synthesis Of Polysubstituted Pyridine And Indeno [1,2-b] Pyrrole Derivatives Based On The Blaise Reaction

Heterocyclic compounds are important organic compounds which are not only present in natural products,but are also widely used in medicine,pesticide and materials.Tandem reaction is a concise and efficient protocol for construction of complex molecules with biological activities and has been widely used in the construction of natural-like heterocyclic skeletons.The reaction of a Reformatsky reagent with a nitrile,known as the Blaise reaction,has long been utilized for the synthesis ofβ-ketoesters andβ-enaminoesters.In recent years,the Blaise reaction intermediates have been trapped with suitable building blocks in a tandem manner,which provided facile access to a great number of heterocyclic compounds.In this thesis,two novel heterocyclic skeletons have been synthesized by the Blaise tandem reaction.This study contains three parts of work.The first part was focus on the Blaise reaction and it’s progress in applications in tandem reaction.In part two,a novel synthesis of2,3,5-substituted and 2,3,4,5-substituted pyridines has been developed.The protocol for 25 polysubstituted pyridine derivatives from the tandem reaction of nitrile,bromoacetic ester and 3-substituted chromone via Knoevenagel-type reaction and subsequent 6πelectrocyclization of the Blaise reaction intermediate and chromone was developed.In part three,nitriles,bromoacetic esters and ninhydrin were employed as raw materials to prepare a series of indeno[1,2-b]pyrrole derivatives.The structures of the products were characterized by ¹H-NMR,¹³C-NMR and HRMS-ESI.The advantages of this reaction include good yields of the products,large functional group tolerance and easily available starting materials.