Asymmetric Synthesis of 2-Benzyl-2-arylindolin-3-ones by Iron-Catalyzed Reductive Benzylation of
Fan Yang1,2,3, Linchun Zhang1, Meiqi Liang1
1Yunnan Key Laboratory of Chiral Functional Substance Research and Application, Yunnan Minzu University, Yuehua Street, Kunming 650504, China.
Abstract:
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.
Related Concept Videos
Benzene to 1,4-Cyclohexadiene: Birch Reduction Mechanism
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
Preparation of Amines: Reductive Amination of Aldehydes and Ketones


