Synthesis Of Arene Fused Six-Membered Cyclic Nitrones Via Copper-catalyzed Intramolecular Cope-Type Hydroamination Reaction

Nitrone has nearly developed for one hundred years.It is not only widely used in building all sorts of important heterocyclic compounds and natural products,but also as a free radical scavenger for medical purposes,widely used in the fields polymerization and biomedicine.The use of nitrone as a free radical capture reagent to treat related diseases has received increasing attention.As intermediate of synthetic alkaloids and natural bioactive molecules,cyclic nitrones play an important role in synthetic chemistry.In recent years,the synthesis methods of nitrone have been emerging,but most of them rely on the traditional non-catalytic synthesis,and catalytic synthesis of chiral nitrones are very rare.Furthermore,most of nitrone compounds is aldonitrone,and the synthesis of ketonitone is more challenging,because the condensation reactions suitable for aldonitrons are usually not suitable for ketonitones.Therefore,it is urgent to develop green,efficient and catalytic methods for the synthesis of chiral ketonitrones.Cope-type hydroamination reaction is the inverse process of Cope elimination reaction.The intramolecular Cope-type hydoamination reaction for synthesis of nitrone is very rare and progress is very slow during the past three decades.This paper is divided into two parts.The first part mainly introduces the reaction of nitrone and Cope-type hydroamination reaction.The second part is the experimental part.Inspired by our recent report on the intermolecular Cope-type hydroamination reaction with cyclopropene,in this work,we proposed and realized the Cope-type intramolecular hydroamination reaction of benzene-,indole,as well as pyrrole-tethered ?-alkenyl oximes for the synthesis of a unique type of chiral six-member benzo-,indolo-and pyrrolo-cyclic ketonitrone 3-methyl-3,4-dihydroisoquinoline N-oxides.Asymmetric induction with chiral bisphosphinel ligands was performed with benzo system,and moderate enantioselectivities were obtained.