Chiral 2-substituted imidazolines are not only privileged scaffolds in many bioactive compounds,but they are also widely used as ligands and catalysts in asymmetric synthesis.However,the synthesis of enantioenriched 2...Chiral 2-substituted imidazolines are not only privileged scaffolds in many bioactive compounds,but they are also widely used as ligands and catalysts in asymmetric synthesis.However,the synthesis of enantioenriched 2-substituted imidazolines is heavily relied on in step-wise synthetic approaches to chiral diamines under relatively harsh conditions.Herein,we present a highly enantioselective addition/hydroamidination of nitriles to allylamines enabled by chiral bis(oxazolinato)rare-earth metal catalysts.This protocol provides a straightforward and atom-economical route to structurally diverse enantioenriched 2-susbtituted imidazolines(in 67 examples up to 99%yield,99%ee)under mild conditions.The utility of the current method is demonstrated by the late-stage modification of complex and bioactive compounds as well as further transformations of products to other important compounds.The preliminary bioactivity study reveals that two of the new chiral imidazolines display a high inhibitory effect onlung cancer cells and hepatocellular carcinoma cells.Moreover, the possible reaction mechanism and originof enantioselectivity were elucidated based onexperimental studies and theoretical calculations.展开更多
基金support from the National Key R&D Program of China(grant no.2022YFA1504301)the National Natural Science Foundation of China(grant nos.22271199,92256303,and 92056107)the Sichuan Science and Technology Program(grant no.2023YFSY0063).
文摘Chiral 2-substituted imidazolines are not only privileged scaffolds in many bioactive compounds,but they are also widely used as ligands and catalysts in asymmetric synthesis.However,the synthesis of enantioenriched 2-substituted imidazolines is heavily relied on in step-wise synthetic approaches to chiral diamines under relatively harsh conditions.Herein,we present a highly enantioselective addition/hydroamidination of nitriles to allylamines enabled by chiral bis(oxazolinato)rare-earth metal catalysts.This protocol provides a straightforward and atom-economical route to structurally diverse enantioenriched 2-susbtituted imidazolines(in 67 examples up to 99%yield,99%ee)under mild conditions.The utility of the current method is demonstrated by the late-stage modification of complex and bioactive compounds as well as further transformations of products to other important compounds.The preliminary bioactivity study reveals that two of the new chiral imidazolines display a high inhibitory effect onlung cancer cells and hepatocellular carcinoma cells.Moreover, the possible reaction mechanism and originof enantioselectivity were elucidated based onexperimental studies and theoretical calculations.
