Study On The Asymmetric Synthesis Of NN Bipyrrole Axial Chiral Compound

N-N biaryl atropisomers are found in many important natural products and drug active molecules,and they are the core skeleton of many ligands and catalysts.In recent years,biaryl atropisomers featured with C-C bond and C-N bond axis have attracted wide attention.However,atropisomers arising from restricted rotation around an N-N bond is largely overlooked.The atroposelective construction of axially chiral N-N atropoisomers remains unexplored.Considering the potential application of N-N atropisomers in natural products and drug design,we propose two strategies to construct N-N biaryl atropisomers,which are summarized as follows:Part one:Construction of N-N atropisomers via Lewis acid catalyzed asymmetric Friedel-Crafts reaction.The asymmetric synthesis of N-N atropisomers was successfully achieved using lewis acid-catalyzed desymmetric Friedel-Crafts reaction of bipyrrole,which providing a simple and efficient method for the synthesis of N-N biaryl atropisomers.In this method,readily available Cu（OTf）₂/BOX,was used to achieve the stereocontrol smoothly,and broad substrate scope was investigated under optimal conditions.The results showcased an excellent generality of the chemistry.Part two:Chiral phosphoric acid catalyzed Paal-Knorr reaction to construct N-N biaryl atropisomers.N-N biaryl atropisomers were constructed by the strategy of de novo synthesis of pyrrole ring,which was catalyzed by chiral phosphoric acid.Exploratory experiments show that this method is suitable for the synthesis of N-aryl atropisomers,and provides a new method with application prospect for the synthesis of N-N biaryl atropisomers.In conclusion,we have developed an enantioselective synthesis of N-N biaryl atropisomers for the first time.N-N biaryl atropisomers with excellent enantioselectivity were efficiently prepared by desymmetrization strategy.It delivers a new path for enantioselective synthesis of N-N biaryl atropisomers.