Construction Of Chromeno-Fused Compounds Via Visible Light Promoted Chan-Lam Reaction And Cycloaddition Cascade Reactions

As one of the most concerned heterocyclic compounds,chromeno-fused compounds widely exist in various bioactive molecules,drug molecules and natural products.The efficient construction of chromeno-fused compounds is one of the most important research subjects in organic synthesis.In addition,the application of visible light,as a green and inexhaustible energy,is a new strategy to realize green chemistry in organic synthesis in recent years.This thesis focuses on the efficient construction of novel chromeno-fused compounds with multiple chiral centers under the condition of visible light and copper（II）salt which catalyzed Chan-Lam coupling reaction,intramolecular[3+2]cycloaddition and[3,3]-rearrangement cascade reactions.The transformation and application of chromeno-fused compounds were investigated and the mechanism of Chan-Lam coupling reaction and[3+2]cycloaddition was deeply discussed by XPS,LC-MS,Hammett and other control experiments.This paper is divided into two parts:In the first part,the strategy of visible light promoted Chan-Lam coupling reaction and intramolecular[3+2]cycloaddition was developed,which could construct chromeno-fused isoxazoline compounds with three chiral centers in one pot in moderate to excellent yields with high diastereoselectivity.The method had the characteristics of catalytic amount of copper salt,mild conditions,simple operation,good compatibility of functional groups and wide scope of substrates.The mechanistic studies showed that visible light promoted both the Chan-Lam reaction and the cycloaddition step.In addition,the reaction was easily performed at gram scales,and could be used to modify the drug molecule estrone and chromeno-fused isoxazoline skeleton was easily introduced into estrone.This method was of great significance for the modification and transformation of natural products and drug molecules.In the second part,with the promotion of visible light,withα,β-unsaturated ketoxime as raw material,a three-step cascade reaction of Chan-Lam coupling reaction/[3+2]cycloaddition/[3,3]-rearrangement was promoted by a catalytic amount of copper salt and photosensitizer.And the chromeno-fused nine-membered heterocycles with four chiral centers were constructed with high efficiency and high diastereselectivity.In addition,the reaction mechanism was deeply discussed:The importance of visible light was proved by switching reaction and control experiment.The important role of singlet oxygen is proved by singlet oxygen capture experiment.The electron-withdrawing group on the cinnamyl benzene ring of N-alkenyl-α,β-unsaturated nitrone facilitated to promote the[3+2]cycloaddition reaction through Hammett experiments.The existence of Cu^I intermediate was proved by X-ray photoelectron spectroscopy（XPS）,while the existence of Cu^II and Cu^IIIintermediates were confirmed by LC-MS.The oxidation potential of nitrone was measured by cyclic voltammetry（CV）,which further proved the correctness of the mechanism.And the reaction mechanism of Chan-Lam coupling reaction was further clarified through a series of control experiments.