Synthesis And Research Of Isochromel Isoquinoline And Benzocycloheptene

It is well-known that cyclic compounds are not only widely found in various natural products and bioactive molecules,but also play an important role in the synthesis of various drug molecules and new materials.Ortho-alkynylbenzaldehydes are a class of indispensable intermediates that can build different polycyclic skeletons,such as the indenones,naphthalenes,and so on.Therefore,it has been widely concerned by researchers.Based on the research of ortho-alkynylbenzaldehydes,we proposed two new synthestic strategies to construct4-?1H-isochromen-1-ly?isoquinoline and benzocycloheptene compounds,respectively.The specific research projects were described as follows:In part one,we have developed an efficient method for the preparation of 4-?1H-isoquinoline-1-ly?isoquinoline derivatives.The synthesis route is composed of two steps:firstly,silver salt is used to catalyze the reaction of ortho-alkylbenzaldehyde in tetrahydrofuran,so that the two molecules of ortho-alkynylbenzaldehydes occurs[3+2]cycloaddition reaction,and form1,5-dicarbonyl isochromene compounds.Then,itfurther react with NH₃ in methanol,and1,5-dicarbonyl unit is dehydrated to form electron-deficient isoquinoline skeleton.In the process of optimizing the yield,in order to simplify the operation steps and avoid the loss,we combined the two processes into one step.After the dimer reaction is completed by the reaction of ortho-alkynylbenzaldehydes,the catalyst is simply filtered out and the solvent is evaporated.The methanol solvent and solution of ammonia in methanol are added into 1,5-dicarbonyl isochromene compounds,and obtained the target product.Sixteen isoquinoline substituted isochromene compounds were prepared by this method,and the yield was up to 31-91%.The advantages of the reaction have mild reaction conditions,simple experimental operations and high yields.In part two,based on the research of ortho-alkynylbenzaldehydes,we develop an effective method for the synthesis of benzocycloheptene compounds with high stereoselectivities and high yields.In 1,4-dioxane,gold?III?and TfOH are used to co-catalyze the reaction of ortho-alkynylbenzaldehydes and cyclopropylene,and control the temperature at 90?C,after 1hour,it can achieve the synthesis of benzocycloheptene derivatives in 22-65%yields.From a mechanistic point of view,this reaction goes through tandem[4+2]cycloaddition/ring expansion reaction of cyclopropene with the dropwise cleavage of the double bond.The reaction features not only mild conditions,and simple experimental operation,the wide scope of substrate.This method provides a simple and efficient method for the construction of benzoheptene compounds.