Enantioselective Synthesis of α-Aryl-α-fluoroketones by CPA-Catalyzed Desymmetrization of 1,3-Indanediones

Herein, we report the use of electrophilic fluorine-containing building blocks─α-fluoro-α-aryl-1,3-indanediones─as substrates for investigating asymmetric catalytic desymmetrization via imine condensation reactions. This method exhibits remarkable compatibility with a broad range of substrates, thereby providing various enantiopure α-aryl-α-fluoro carbonyl compounds with high enantioselectivities and yields. Density functional theory (DFT) calculations indicate that F–H interactions between the F atom of the α-fluoro-α-aryl-1,3-indanediones and the NH group of 5-aminopyrazole, as well as π–π stacking interactions between the two coupling partners, likely play crucial roles in controlling the enantioselectivity of this transformation.