Construction Of N-heterocycles Via Tandem Cyclization And Functionalization Reactions Of 2-nitro-1,3-enynes

N-Heterocyclic compounds occupy a very important position in organic chemistry,which are also commonly used in natural products and pharmaceutical intermediates.Because of their unique structural characteristics and potential biological activity,N-heterocyclic compounds have an important application value in the fields of medicine,pesticides,and materials and so on.Pyrrole is one of the important N-heterocyclic compounds.It's widely used in perfumes,dyes,natural compounds,clinical drugs,medicines,pesticides,and materials due to its low toxicity and unique biological activity.For examples,many anti-inflammatory drugs,anti-tumor drugs,xylose ester flavors,chlorophyll and alkaloids contain pyrrole structural units.Isoxazole is also an important N-heterocyclic compound,which is a common structural unit in many drug molecules and pesticides.Many Isoxazole derivatives show broad-spectrum biological activities,such as anti-cancer,anti-viral,anti-microbial,anti-inflammatory,anti-fungal,and some other pharmacological activities.1,3-Enyne is an important raw material for the synthesis of heterocyclic compounds,widely used in organic synthesis.Synthesis of heterocycles via tandem cyclization of enynes is a common efficient method.Recently,great progresses have been made on the synthesis of heterocycles via tandem cyclization of enynes.Herein,we study the tandem cyclization/functionalization of 2-nitro-1,3-enynes to provide 3kinds of functionalized pyrrole derivatives and a new route to isoxazole derivatives.This thesis mainly covers the following four parts:(1)Trifluoromethyl substituted N-containing heterocycles are one of the most popular organic compounds.The first part describes an effective method for the synthesis of fully substituted trifluoromethylpyrroles.This method covers the catalytic system of Cu(OAc)₂·2H₂O and[Cp^*Rh Cl₂]₂,using Togni's reagent(II)as the precursor of trifluoromethyl free radical.The mechanism involves the cascade aza-Michael addition/trifluoromethylation cyclization/oxidation reaction of 2-nitro-1,3-enynes.(2)Organic azides are important chemical raw materials and intermediates,which are widely used in medicine,biology,and material science.The second part of this paper provides a method for the synthesis of fully substituted azido pyrrole derivatives from 2-nitro-1,3-enynes,amines,and TMSN₃.The possible reaction mechanism involves the continuous tandem aza-Michael addition,copper-mediated intramolecular cyclization,Mn-catalyzed free radical azide and oxidative aromatization process.The reaction showed high regioselectivity,wide substrate scope,and mild reaction conditions.In addition,the synthetic application of fully substituted azido pyrrole was examined.The azido pyrrole could be easily converted to the corresponding free amine via reduction reaction in good yield.(3)Sulfonyl heterocycles are a key component of drug molecules and have been widely used in medicinal chemistry.They have unique biological activities and physical and chemical properties.In the third part of this paper,a series of benzenesulfonyl substituted isoxazole derivatives were prepared by copper(II)catalyzed three-component tandem cyclization reaction of 2-nitro-1,3-enynes,amines,and sodium benzenesulfinates.This method shows good reaction efficiency,chemical selectivity,as well as a broad substrate scope.The mechanism may involve tandem aza-Michael addition,intramolecular cyclization,sulfonylation,and oxidative aromatization.(4)Nitroso heterocyclic compounds are a very important class of organic compounds and intermediates,which are widely used in organic synthesis.The fourth part of this paper studies the Pd-catalyzed tandem cyclization reaction of 2-nitro-1,3-enynes and aromatic amines through Michael addition,intramolecular cyclization,proton transformation,dehydration,and aromatization.It provides an effective new method for the synthesis of nitrosopyrroles.