Study On Asymmetric Allylation Of Electron-riched Heterocyclic Compounds

Unsaturated lactones are the key backbone of many active drugs and natural products,which have attracted widespread attention in the field of medical chemistry due to the extensive pharmaceutical and biological activities.Traditionally,people often employed chiral resolution technique to obtain heterocyclic lactones with chiral groups.The operation process is relatively complicated.For another,this method leads to low theoretical yield and low atom economy.Moreover,the asymmetric functionalization of heterocyclic lactones also confronted many difficulties such as poor chemoselectivity,high catalyst loading,and insufficient reaction conditions.In this paper,a Friedel-Crafts type electrophilic allylic substitution of electron-rich heterocyclic lactones by catalyzing the asymmetric allyl synthesis is realized.Under the induction of chiral phosphoramidite ligand,branched allylated derivatives are obtained with high yields with excellent enantioselectivities.This article contains the following two parts:The first part mainly introduces the iridium-catalyzed asymmetric allyl synthesis reaction of 4-hydroxycoumarin.Carreira phosphoramidite is used as a chiral ligand to achieve a Friedel-Crafts type allylation reaction with high enantioselectivity under the catalysis of Iridium(I)complexation.The system can be converted into a highly specific allyl coumarin derivative(up to 98% yield and > 99% ee)under the mild condition with high yield.This type of chiral building blocks occupies an important position in drug synthesis.In addition,both large-scale experiment and chemical transformation proved the potential practicability and applicability of the methodology.The second part is an extension of the above work,which introduces the asymmetric allylic substitution reaction of pyrone derivatives catalyzed by Iridium complex.We use 4-hydroxy-2-pyrone and branched cinnamyl alcohol as raw materials.Under the optimal condition,we have synthesized more than 20 optically pure allyl pyrones with moderate to excellent yields and ee values.The derivatives are commonly found in the substructures of natural products and synthetic pharmaceuticals.This method not only successfully achieved the directed asymmetric electrophilic allylic synthesis of pyrone compounds under the mild condition,but also is expected to enrich the molecular library of pyrone drugs through the further chemical modification.This series of research work not only expanded the scope of research in the asymmetric catalysis,but also provided a vital technical basis for the subsequent research on asymmetric functionalization of heterocyclic lactone derivatives.