Synthesis Of Nitrogen-containing Polycyclic Compounds By Ring Expansion Reaction Participated By Electron-deficient Alkynes

Due to the relatively long distance of bond position and low interaction force,nitrogen-containing medium-sized cyclic compounds are in a disadvantageous position in terms of thermodynamics and kinetics.Moreover,due to the influence of regioselectivity and stereoselectivity of substituents,it is not easy to obtain the target products.In this paper,the tertiary nitrogen atom in spiro[indoline-3,3’-pyrrolidine]structural unit constructed by L-proline,isatin and chalcone was used to expand the pyrrolidine ring by nucleophilic addition reaction with electron deficient alkynes and several nitrogen-containing polycyclic compounds with unique structure were obtained.This paper mainly discusses the following three parts:1.We have investigated the one-pot two-step reaction of L-proline,isatins,chalcones and methyl propiolate or dimethyl but-2-ynedioate in refluxing methanol.In the reaction,44 diverse spiro[indoline-3,7’-pyrrolo[1,2-a]azepines]compounds were synthesized in satisfactory yields and with high diastereoselectivity.The reaction mechanisms included domino[3+2]cycloadddtition reaction of azomethine ylide with chalcone and ring-expansion reaction of in situ generated spiro[indoline-3,3’-pyrrolizine]with electron-deficient alkynes.This reaction had the advantages of using readily available materials without catalyst,widely variety of substrates,molecular diversity,good yields and high diastereoselectivity.2.We have investigated the three-component reaction of L-proline,isatins and chalcone and the sequential domino annulation reaction with methyl propiolate in refluxing acetonitrile and synthesized 36 diverse hexahydro-and octahydropyrrolo[1’,2’:1,2]azocino[4,5-c]quinolines compounds in medium and above yields.This reaction combined the novelty of the 1,3-dipolar cycloaddition and-nucleophilic addition of the tertiary amine to the electron-withdrawing alkynes and developed a sustainable synthetic method for the synthesis of polycyclic azocine derivatives.This one-pot two-step reaction has the advantages of using readily available materials,operational simplicity,molecular diversity,and good yields.This reaction not only exploited the versatile reactivity of alkyl propiolates in cycloaddition reactions but also provided convenient synthetic protocols for complex polycyclic systems.3.We have studied the one-pot two-step reaction of L-proline,isatins,2’-hydroxychalcone and methyl propionate in refluxing methanol or acetonitrile.This reaction achieved an unexpected various cycliclation and expansion products.The key to the reaction was the reactivity of the anion center and the nature of the solvent which led to the cleavage of C-N bonds in different ways in different solvents.The reaction mechanisms included tandem[3+2]dipole cycloaddition,nucleophilic addition,and ring extension.This reaction provided a special idea for the synthesis of more complex nitrogen-containing polycyclic compounds,and expanded the method of synthesizing nitrogen-containing polycyclic systems.