Asymmetric Synthesis of 2-Benzyl-2-arylindolin-3-ones by Iron-Catalyzed Reductive Benzylation of 2-Aryl-3H-indole-3-ones

In this work, we developed an iron(II)-catalyzed asymmetric reductive benzylation of 2-aryl-3H-indole-3-ones using benzyl bromides. In the presence of FeBr₂, (R)-5-CF₃-Pyox-Ph, acetic acid as an additive, and manganese as the reductant, the reaction afforded 2-benzyl-2-arylindolin-3-ones in high yields (up to 97%) and excellent enantioselectivity (up to 96:4 er). This protocol, which demonstrates a broad substrate scope and good functional group tolerance, not only offers a novel strategy for the enantioselective synthesis of C2 quaternary indolin-3-ones but also provides new insights into the application of iron catalysis. Furthermore, a DFT study revealed that the high enantioselectivity is primarily driven by steric effects; a high-spin (sextet) iron catalyst accelerates the asymmetric reductive coupling reaction.