Regio- and enantioselective umpolung gem-difluoroallylation of hydrazones via palladium catalysis enabled by N-heterocyclic carbene ligand

Installation of difluoroalkyl groups while also imparting stereochemical information is mostly only possible with organocatalytic methods that activate carbonyls. Here the authors show a method to perform an difluoroallylation of hydrazones, forming a masked amine stereocenter, via palladium- and N-heterocyclic-carbene catalysis. The enantioselective construction of C-CF2R (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 alpha/gamma- 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.