Annuloselectivity Of Cyclic Imines,Arynes And Carbon Dioxide

Annulation is an important protocol for the preparation of polycyclic compounds.As that the properties of polycyclic compounds are determined by the ring-size,it is particularly significant to modulate the annulation and control the annuloselectivity for the cyclization lichipins.Imines play a crucial role as intermediates in organic synthesis and various named reactions.Among them,representative N-alkyl cyclic imines such as 3,4-dihydroisoquinoline and N-aryl cycloimide like dibenzo[b,f][1,4]azapyridine,exhibit unique nucleophilicity,steric hindrance,and other chemical properties.As a result,these compounds show distinctive annuloselectivity in annulation reactions.Generally,3,4-dihydroisoquinoline tends to undergo[2+2+2]three-component annulation,while dibenzo[b,f][1,4]azapyridine tends to undergo[2+2]cycloaddition reactions.Arynes are highly reactive organic compounds and are extensively used for synthesizing polysubstituted benzene derivatives.To generate benzyne in situ,trifluoromethanesulfonic acid 6-（trimethylsilyl）phenyl ester is employed,and the TMS groups are removed using fluoride.Nucleophiles readily attack aryne molecules,forming 1,3-zwitterionic intermediates with benzene carboanions.These intermediates exhibit strong nucleophilicity and can capture various electrophiles,including inert substances such as CO₂gas.Although numerous studies have demonstrated the ability of arynes to activate CO₂for generating high-value products,there are currently no reports of selective annulation that binds to cyclic imines.Herein,we focuses on the selective cyclization of3,4-dihydroisoquinoline or dibenzo[b,f][1,4]azapyridine with aryne and CO₂.The research findings indicate that 3,4-dihydroisoquinoline undergoes a three-component[2+2+2]annulation with arynes and CO₂,affording tetracyclically fused benzoxazolinone.In contrast,dibenzo[b,f][1,4]azapyridine only undergoes a[2+2]cycloaddition reaction with arynes and cannot capture CO₂to generate the corresponding oxazolinone.As a N-alkyl imines,nucleophilicity of 3,4-dihydroisoquinoline are much higher than that of N-aryl dibenzo[b,f][1,4]azapyridine.The stronger the nucleophilicity,the easier it is to capture CO₂during the reaction.Additionally,the steric hindrance of dihydroisoquinoline is less than that of dibenzoazazepine,allowing for sufficient space to accommodate CO₂molecules during the annulation.In the absence of CO₂,the reaction system of the three-component annulation of 3,4-dihydroisoquinoline produces specifically the[2+2]cycloaddition reaction product.Due to its active reaction nature,the reaction system is more complex,and therefore,the introduction of inert substance CO₂is crucial to achieving a similar effect of dibenzo[b,f][1,4]azapyridine.The substituent effect has a great influence on the annulation of dihydroisoquinoline:1)the electron-rich dihydroisoquinoline can promote the reaction,whereas electron-deficient dihydroisoquinoline obviously inhibit the conversion.2)the steric hindrance of dihydroisoquinoline obviously inhibit the annulation.3.Electron-deficient aryne is much more reactive than that of electron-rich arynes,verifying that the rate-limiting step might be the first step.4.The electronic and steric effect of substituent in aryne obviously control the regioselectivity of annulation.As a new method for synthesizing benzoxazolinone,compared with other methods,it has significant advantages in mild conditions,strong adaptability and easy availability of raw materials.At the same time,the derivatization reaction of the product benzoxazolinone was also completed,and o-aminobenzoic acid derivatives with potential application value were prepared by various Grignard reagents.