Enantioselective construction of chiral gem-difluorinated C2-quaternary indoline via dual MgSO₄–CPA-catalyzed asymmetric Mannich reactions

By: Xin-Chun Wang, Xing-Pin Wei, Chang-Peng Zou, Tao Ma, Yonghui He, Ganpeng Li, Xiao-Jing Zhao

DOI：https://doi.org/10.1039/D3QO02085A

Published：2024-01-10

Abstract:

The construction of the –CF₂ moiety has garnered significant interest from the organic synthesis and medicinal chemistry communities. Herein, the synthesis of 2-(3,3-difluoro-2-phenylindolin-2-yl)-1-phenylethan-1-one scaffolds through asymmetric Mannich reactions between 3,3-difluoro cyclic ketimines and simple ketones is described. This process provides a broad range of chiral gem-difluorinated C2-quaternary indolines. The excellent reactivity and stereocontrol can be attributed to the dual MgSO₄–CPA catalysis system. The adducts obtained could be readily converted into various synthetic blocks.