Rhodium Catalyzed N-H Bond Reaction Of Asymmetric Carbene Insertion Into Indole/Carbazole To Construct C-N Axis Chiral Compounds And Their Applications

Axial chirality is a special kind of chirality that results in compounds having axial chirality when the rotation of a single bond in a compound is hindered.Axially chiral compounds are widely used in asymmetric catalysis,materials chemistry and pharmaceuticals.The most common axial chiral compounds are the C-C axis chiral compounds,while the C-N axis chiral compounds are rare.Therefore,the construction of C-N axis chiral compounds has certain practical significance and challenges.Indole and carbazole are the most common nitrogen-containing heterocyclic compounds and have long played an important role in the pharmaceutical field.We therefore chose to use aryldiazo to indole or carbazole asymmetric N-H bond insertion to construct C-N axis chiral compounds.In the process of studying the insertion reaction of diazo to indole,it is found that C-H insertion reaction is more likely to occur at carbon 2,carbon 3,and carbon 6 of indole.Therefore,the control of chemical regioselectivity and enantioselectivity of the reaction are two major challenges.We used 1a and 2a as template substrates,and finally determined the optimal conditions by screening the catalyst,solvent,temperature,substrate ratio and concentration:the catalyst was Rh₂（S-NTTL）₄,the solvent was DCM,and the temperature was 30℃,Substrates ratio 1a:2a=1:1.3,1a concentration is 0.1 mmol/m L.Under optimal conditions,the yield can reach 90%,and the ee value can reach 96%.In the process of studying the insertion reaction of diazo to carbazole,we used 4a and 2b as template substrates,and finally determined the optimal conditions by screening the catalyst,solvent,temperature,substrate ratio and concentration:the catalyst is Rh₂（S-PTTL）₄,the solvent is DCM,the temperature is 30°C,the substrates ratio is 1a:2a=1:2,and the concentration of 4a is 0.05 mmol/m L.Under optimal conditions,the yield can reach 83%,and the ee value can reach 99%.We further make the obtained C-N axis chiral products into ligands,which can be used to catalyze other reactions.Under optimal conditions,the simple and readily available diazonium compounds are catalyzed by chiral rhodium to form rhodium carbene,which then undergoes an intermolecular asymmetric N-H bond insertion reaction with indole/carbazole to generate a C-N axis chiral linkage with high corresponding selectivity Aryl compounds.The method has the 99%atropoversion selectivity,90%yield,good tolerance of functional groups and mild reaction conditions,which provides a new method for the development of novel ligands.