Silver-catalyzed Asymmetric Cycloaddition Reactions Of Activated Isocyanides

N-heterocycles are a kind of very important molecular skeletons,which widely exist in natural products,bioactive molecules and drugs,and also have extensive applications in organic synthesis and material chemistry.In view of this,the construction of nitrogen heterocycles is an important research goal in the field of organic synthesis.In recent years,the asymmetric cycloaddition reaction of activated isocyanides with many electrophilic π-system compounds catalyzed by transition metals and organic catalysts has been widely studied,which has become an important method to construct chiral nitrogen heterocyclic compounds.In this paper,the synthesis methodology of two new types of nitrogen-containing heterocyclic compounds has been developed around the asymmetric cycloaddition reaction of activated isocyanides,as follows:Part I: Silver-catalyzed asymmetric [3+3] cycloaddition of activated isocyanides was developed to construct chiral 1,2,4-triazine compounds via kinetic resolution.This method starts from the easily available azomethylene imines and activated isocyanides,affording a series of chiral 1,2,4-triazine compounds in excellent yields with stereoselectivities under mild conditions.Through the research of synthesis application,it shows that a series of chiral nitrogen heterocyclic compounds can be generated,which provides a new idea for the synthesis of chiral nitrogen heterocycles by the cycloaddition reaction of activated isocyanides.Part II: Silver-catalyzed asymmetric [3+2] cycloaddition of activated isocyanides was developed to construct C-N axis chiral and polycentrically chiral nitrogen-containing heterocyclic compounds via desymmetrization.Compared with previous studies,we have constructed nitrogen-containing heterocyclic compounds with multiple chiral centers through the same catalytic system in one step,and the stereoselectivity of which is excellent.The stability of the method was also proved by amplification reactions and derivations.To sum up,this paper has developed the catalytic system of silver and chiral phosphine ligands which realized the asymmetric [3+3] cycloaddition of activated isocyanides for the first time,through which a series of chiral 1,2,4-triazine compounds were constructed.Then,this catalytic system was used to activate isocyanides to construct C-N axis chiral nitrogen heterocyclic compounds through [3+2] cycloaddition for the first time,and may provide a new way to activate the asymmetric cycloaddition reaction of activated isocyanides.