Research On Radical-Involved Intramolecular Asymmetric C-H Amination

Chiral N-containing heterocycles are important motifs widely displayed in natural products,pharmaceuticals and bioactive molecules,so the development of efficient asymmetric catalysis methods to access those compounds has attracted much attention from synthetic chemists.Compared to the well-documented classical methods,the asymmetric C-H amination has high reaction efficiency and high atom economy;and for these reasons,the asymmetric C-H amination has become a hot topic in recent years.However,the asymmetric C-H amination successfully developed commonly involves transition metal-catalyzed C-H bond activation or metallonitrene insertion into C-H bond,where noble metals are requisite as catalyst and the substrate scope/accessibility of starting material in these reactions often suffers from some limitations.Therefore,it is highly desirable to develop ample efficient asymmetric C-H amination reactions for overcoming the defects existed in current methods.Liu's group has successfully developed a dual catalytic system of copper/chiral phosphoric acid(Cu/CPA)to realize the asymmetric radical 1,2-difunctionalization of unactivated alkenes.Inspired by these work,we envision that Cu/CPA catalytic system might be applied in radical involved intramolecular asymmetric C-H amination to provide an efficient approach to chiral N-containing heterocycles.In this work,radical-involved intramolecular asymmetric amination of unactivated C-H bond was successfully developed after systematic screening of reaction conditions.The experimental results showed that the choice of suitable oxidants,additives and modified CPAs plays an important role in obtaining good reaction efficiency and high enantioselectivity.In addition,a variety of substrates bearing different functional groups were well-tolerated in this reaction,which potentially provides an efficient tool to synthesize chiral pyrrolidine derivatives.In the end,the mechanism studies indicated that the active benzylic radical species resulting from intermolecular HAT process might be the key intermediate in the context of the transformation.