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Despite paramount applications of chiral trifluoromethylated compounds in medicinal chemistry and materials science, limited strategies have been developed for catalytic asymmetric synthesis of such valuable fluorinated structures. Here, we report a nickel catalyzed enantioselective dicarbofunctionalization of inexpensive industrial chemical 3,3,3-trifluoropropene (TFP) with readily available tertiary alkyl and aryl iodides. The reaction overcomes the β-F elimination side reaction of TFP, and proceeds efficiently under mild reaction conditions. The protocol possesses advantages, such as synthetic convenience, high enantioselectivity, and excellent functional group tolerance, providing rapid and straightforward access to chiral trifluoromethylated compounds of medicinal interest., (© 2022. The Author(s).)

The enantioselective construction of C-CF 2 R (R: alkyl or fluoroalkyl) bonds has attracted the attention of synthetic chemists because of the importance of chiral fluorinated compounds in life and materials sciences. Catalytic asymmetric fluoroalkylation has mainly been realized under organocatalysis and Lewis acid catalysis, with substrates limited to carbonyl compounds. Few examples using transition-metal catalysis exist, owing to side reactions including decomposition and isomerization of fluoroalkylating reagents. Herein we report umpolung asymmetric difluoroallylation of hydrazones with 3-bromo-3,3-difluoropropene (BDFP) under palladium catalysis. Difluoroallylation products having quaternary chiral carbon centers are afforded in good yields with high α/γ- and enantioselectivities. The usefulness of the reaction products is demonstrated and an inner-sphere mechanism of the reaction is proposed. The use of chiral N-heterocyclic carbene as ligand is the key for the selectivities as well as the productivity of the reaction., (© 2021. The Author(s).)