A Study On Construction Of Pyrrole And Pyridine Rings From Chlorocyclopropanes

As the core structures,multi-substituted pyrrole and pyridine rings exist widely in many natural products and synthetic drugs with vital research value.Nitrones derived from secondary amines,and methylimide ylides derived from imides as common 1,3-dipoles can undergo [3 + 2] cycloaddition reactions with olefins to construct nitrogen-containing heterocyclic compounds with diverse structures.These nitrogen-containing heterocyclic compounds play an important role in the fields of materials,medicine and biology,and they can be used as intermediates to construct natural products,pharmaceutical molecules and biomolecules.Although various methods are developed for the preparation of pyrrole and pyridine rings,few previous reports are referred to the rearrangement aromatization reactions of nitrogen-containing bicyclic compounds catalyzed by acids or bases.Therefore,this thesis is concentrated on the synthesis of azabicyclic compounds starting from chlorocyclopropanes containing electron-withdrawing substituents at the 1,2-sites that have been developed in our group,and the rearrangement aromatization reactions of the azabicyclic compounds.The main research contents are as follows:1)This thesis describes that the reactive cyclopropene intermediate,generated in situ from alkyl 2-aroyl-1-chlorocyclopropane carboxylate,readily undergoes a [3 + 2] cycloaddition reaction with nitrones to afford bicycloisoxazoline compounds with high regioselectivity(up to 10:1).Treatment of the cycloaddition products with Lewis acid leads to a rearrangement aromatization to give multi-substituted pyrroles in high yields under mild conditions.Further experiments demonstrate that the crude products can be directly used for the following rearrangement without isolation to afford multi-substituted pyrroles through a one-pot procedure in up to overall 82% yield.In addition,a plausibe reaction mechanism was suggested.This method has some advantages such as available starting materials,wide spectrum of substrates,good yields,mild reaction conditions,easy separation and without using precious metals.It provides a new synthetic method for a variety of multi-substituted pyrrole compounds.2)This thesis describes that the symmetrical reactive cyclopropene intermediate,generated in situ from 1,2-diarylacyl-1-chlorocyclopropane,readily undergoes a [3 + 2] dipolar cycloaddition reaction with methylimine ylides derived from imides to afford azabicyclo[3.1.0]hexanes.Further experiments demonstrate that the cycloaddition products can be directly used for the following rearrangement without isolation.Treatment of the crude products with an oxidant and base readily afford multi-substituted pyridines through a one-pot procedure in up to overall 76% yield.Meanwhile,a plausible reaction mechanism was proposed.This reaction provides a new way for the synthesis of polyfunctional multi-substituted pyridine compounds.