Bioactive Scaffolds Construction Via [i,3]-Sigmatropic Rearrangement Of N-Phenoxyamides (i=2,3)

In recent years,N-phenoxyamides have been verified to be a versatile substrates.It can be transferred into diverse of phenols or oxa-heterocycles by treating with different coupling partners.However,most of the reactions are catalyzed by transition metals.Most of the transition metals are usually expensive.Besides,in many cases,special additives and cocatalysts are also critical to promote transformations.All of those bring inconvenience to operators as well as violate the conception of green chemistry.Obviously,alternative metal-free pathways to develop N-phenoxyamides chemistry are highly appealing.N-O-cleavage-assisted transformations are favored due to the intrinsically weak and highly polar O-N bond.This thesis focus on developing mild metal-free rearrangement reactions to build bioactive structures based on the broken of O-N bond of N-phenoxyamides.The following two parts of research work have been carried out.1.Selenoenzyme inspired para-amination of phenolsSelenium-containing small molecules,such as ebselen and its analogues,have exhibited important antioxidant activity as selenoenzyme glutathione peroxidase(GPx)mimics.Inspired by the redox versatile of ebselen,we realized the para-amination of phenols by incorporating a transient Se-N into N-phenoxyamides.Screening of different organoselenium indicated the phenylselenenyl bromide was the best catalysis to covert the reaction.A combination of experimental and computational studies suggested that the organoselenium compound catalyzes two consecutive[2,3]-sigmatropic rearrangements under mild reaction conditions.Howerver,we only obtained the S-N preserved products when the sulfur variants were used.What's more,the migration of acetamide on 1v under biocompatible conditions enabled the formation of an AIEgens product(2v),which contributes it to be a useful tool in chemical biology.2.Benzofurans and benzoxazoles synthesis via sigmatropic rearrangement of N-phenoxyamidesIn this part,encouraged by the DFT calculations on the[3,3]-sigmatropic rearrangements,we report a unified rearrangement to synthesize benzofurans and benzoxazoles by treating N-phenoxyamides with compounds containing an sp-hybridized carbon(bromoalkynes,keteniminiums or cyanogen bromide).On the basis of a series of experimental and computational studies,we revealed that the reactions proceeded through a facile Claisen-like[3,3]-sigmatropic rearrangement/annulation process.This process did not need metal catalysts.The salient features of this reaction include no need of metal catalysts,wide substrate scope,mild reaction conditions and good reaction kinetics.The generality of the process was illustrated by the late-stage diversification of natural products,estrone and an approved drug.Besides,benzoxazole benzenesulfonamides,which have been identified as inhibitors of human fructose-1,6-bisphosphatase(hFBPase-1),were synthesized successfully under mild reaction conditions.