Copper-Catalyzed Asymmetric Conjugate Addition For The Construction Of Chiral Hydrobenzofuran And Pyrroloindole Scaffolds

Hydrobenzofuran and pyrroloindole are the core scaffold of various natural products or pharmaceuticals.New catalytic asymmetric synthesis methods for the efficient construction of similar structure is one of the research hotspots in the field of organic synthesis,but at the same time challenging.In this dissertation,two novel strategies are developed by copper-catalyzed asymmetric conjugate addition to construct the chiral hydrobenzofuranones and pyrrolo[1,2-a]indoles scaffolds.1.Asymmetric intramolecular conjugate addition of cyclohexadienones-tethered imino esters by Cu(Ⅰ)/chiral P,N-ligand,with moderate to excellent yields(up to 90%),excellent diastereoselectivity(up to>20:1 dr),and excellent enantioselectivity(up to 97%ee)to construct chiral 3-amino-hydrobenzofuran-2,5-dieno scaffold,and at the same time realize the desymmertrization of prochiral cyclohexadienones.2.Asymmetric conjugate addition/lactamization cascade reaction of 2-nitrovinylindoles with N-acylpyrazoles catalyzed by Cu(Ⅰ)/chiral P,P’-ligand,with moderate to excellent yield(up to 94%),excellent diastereoselectivity(up to 19:1 dr)and good enantioselectivity(up to 86%ee)to construct a series of chiral pyrrolo[1,2-a]indoles scaffolds with some different substituents.