Enantioselective Synthesis of Chiral 2,2-Difluoro-spiroindanone-dihydroquinazolinones by CPA-Catalyzed Cyclization Reactions.

The synthesis of chiral -difluorinated spiro-heterocyclic compounds continues to be a significant challenge in organic chemistry due to their widespread applications across various fields. Therefore, efficient asymmetric approaches for the synthesis of -difluorinated spiroindanone-dihydroquinazolinones are particularly valuable, especially in the industrial manufacturing of chiral fluorinated drugs. Herein, we developed the CPA-catalyzed asymmetric enantioselective cyclization reactions of -difluoroalkyl 1,3-indandiones with anthranilamides to achieve various chiral 2,2-difluoro-spiroindanone-dihydroquinazolinones in good to high yields with excellent enantioselectivities. Moreover, the mechanism experiment proved that the -difluoro substitution pattern promotes the reaction.