Asymmetric Hetero-Diels-Alder Reactions Of Vinyl Azides:Synthesis Of Fused-ring Azides

Vinyl azides is a kind of compound containing both alkenyl and azide groups,whose carbon-carbon double bond conjugates to the azide group.The azide group,a recognized electron donor,can polarize and activate the alkenyl because of the conjugation structure.Thus,vinyl azides are crucial synthons,which have chemical activity in different types of reactions and can be effectively converted into nitrogen containing heterocycles or functionalized amides.Vinyl azides can be used not only as azide compounds,but also as free radical receptors,enamine-type nucleophiles and even electrophiles in the syntheses of nitrogen heterocycles and their derivatives.In most reactions,vinyl azides acted as 3-atom(CCN)synthesizers in organic synthesis by rapidly releasing a molecule of nitrogen as reaction driving force.However,there are very limited reports on the retention of the azide group in the reaction involving vinyl azides.This transformation is very challenging because of the competitive reaction of releasing nitrogen.Therefore,we hope to retain the azide group in the reaction involving vinyl azides,and obtain valuable chiral organic azides through asymmetric catalysis.Based on this problem,the following two parts of work have been carried out:In the first part,we developed a highly efficient chiral nickel(Ⅱ)/N.N’-dioxidecatalyzed asymmetric HDA reaction of vinyl azides and active ketone carbonyl compounds to synthesize of chiral fused-ring azides.The important feature of this reaction includes quick building molecular complexity from easily available materials,100%atom-economy,and excellent enantioselectivities.The efficient synthetic method for such azide group retention has potential applications in the field of drug synthesis and development.In the second part,the feasibility of asymmetric HDA reaction between vinyl azides and simple aldehydes(4-nitrobenzaldehyde)was investigated.The cyclized product was obtained in 56%yield with 91%ee.Detailed optimization of reaction conditions need to be carried out in further research.Simultaneously,asymmetric HDA reaction of vinyl azides and imine was also carried out.Though the product could be obtained with excellent yield,it is still necessary to search for a suitable catalytic system which could regulate enantioselectivity and diastereoselectivity for this reaction.