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

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.