| The chiral coumarin skeleton is a common structural unit in drug molecules and natural products.In addition,it plays an important role in natural products,drugs and functional materials.Therefore,the development of synthetic method for chiral coumarin skeleton with high enantioselectivity and efficiency is of great academic significance and has broad application prospect,thus has attracted the research interest of many synthetic chemists.Among the reported synthetic methods,the strategy starting from 3-substituted coumarin is the most widely used one.In this thesis,we have developed two new asymmetric catalytic methods using 3-substituted coumarins as starting materials,which provide two new routes for asymmetric construction of chiral coumarins.(1)We first developed a catalytic asymmetric [4+2] cycloaddition of3-aroylcoumarins with 2,3-butadienoate.Using 10 mol% β-ICD derivatives as the chiral Lewis base catalyst,with ethyl acetate as solvent,the reaction could afford the desired dihydrocoumarin-fused dihydropyranones derivatives in 80-97% yields and up to 90% ee values at 0 ℃.The method has the advantages of using easily-available starting materials and mild reaction conditions,and can be scaled up to gram scale without loss of enantioselectivity.The derivative potential of the corresponding product has been demonstrated by the deprotection of the benzyl ester to the corresponding free carboxylic acid.(2)Starting from 3-nitrocoumarin and methyl 2-phenylisocyanate acetate,we used chiral diphenylethylenediamine-derived tertiary amine-tetrasquara acid as bifunctional catalyst,the targeted conjugated addition products can be obtained with up to 83% ee value at room temperature in 1,2-dichloroethane.This reaction is characterized by mild condition and simple synthetic operation.At present,the subsequent condition optimization and substrate scope investigation are still under progress. |
