Study Of Inverse Electron Demand Diels-Alder Reaction In The Construction Of Bicycles[3.2.2] Skeleton

The skeleton of the bicycles[3.2.2]core is widely present in natural products such as acremoxanthone A,beticolin 1,herbalidal,tubingensin B,etc.these unique skeleton structure and biological activities have aroused the interest of synthetic chemists,and they are interested in directly completing this skeleton.The construction of the skeleton will help us to synthesize and research natural products containing this kind of skeleton.In view of the previous synthetic research on such natural products,we plan to complete the construction of the skeleton of the key bicycles[3.2.2]core with the strategy of inverse electron demand Diels-Alder reaction.Since its discovery,the inverse electron demand Diels-Alder reaction has undergone a wealth of development,and has been researched and applied in methodology,biochemistry,and material chemistry.Among them,many research groups have proposed different schemes for Lewis-catalyzed asymmetric cycloaddition.In this paper,the all-carbon inverse electron demand Diels-Alder reaction between methyl 5-oxo-5H-benzo[7]annulene-6-carboxylate as an electron-deficient dienophile and electron-rich dienophile catalyzed by Lewis acid is studied.With good yield and selectivity,a carbon skeleton structure with multiple continuous stereo centers is obtained.We first used methyl 5-oxo-5H-benzo[7]annulene-6-carboxylate and cyclopentadiene as the template reaction to explore the optimal conditions of the reaction,and confirmed the product through the Graphic of the crystal,and found different Lewis acid has certain control over the ratio of endo/exo of the product.Then we carried out the exploration of substrate expansion,and we conducted preliminary research on the dienophiles that can construct this kind of framework structure which found that this reaction has good reactivity for five-membered ring and six-membered ring dienes as diolefins,and the product skeleton structure has been characterized by X-ray diffraction,two-dimensional NMR and other means.This reaction provides a new method for the rapid construction of compounds with bicycles[3.2.2]structures which provides some interesting dienophile cases for the study of the inverse electron demand to Diels-Alder reaction.