Catalyzed Asymmetric Michael Additions of 1‐Pyrroline Esters with β‐Fluoroalkyl Alkenyl Imides and Azodicarboxylates

The asymmetric Michael addition reactions of 1-pyrroline esters with β-fluoroalkyl alkenyl imides and dialkyl azodicarboxylates catalyzed by the AgOAc/Ph-phosferrox or CuOAc/(R)-BINAP complex have been developed. A series of chiral 1,5,5-trisubstituted pyrroline ester derivatives have been obtained in 53%-90% yields with 80%-99% ee's and all > 20:1 dr. The gram-scale synthesis and synthetic application of the chiral trifluoromethylated 1-pyrroline adducts were exhibited: the pyrrolizidin-3-one analogue was first synthesized with 94% ee and > 20:1 dr through two steps of hydrolysis and reductive cyclization; the pyrrolidine and lactam derivatives were also successfully provided under the reducing conditions of NaBH₃CN and Pd/C─H₂, respectively.