Enantioselective Construction Of 1H-Isoindoles Containing Tri-and Difluoromethylated Quaternary Stereogenic Centers Via Palladium-Catalyzed C-H Bond Imidoylation

Isocyanide is an important reactive reactant with a divalent negatively charged carbon atom.In recent years,isocyanide-based free radical reactions,multi-component reactions,cycloaddition reactions and transition metal catalyzed insertion reactions have received extensive development.Due to the high efficiency,high selectivity and diversity of the palladium-catalyzed insertion reactions,isocyanides were successfully applied in the synthesis of diverse nitrogen-containing heterocycles,natural products and bioactive molecules.Organic heterocyclic compounds containing fluorine atoms have a wide range of applications in agriculture and medicinal chemistry.An intermolecular enantioselective synthesis of 1H-isoindoles containing tri-and difluoromethylated quaternary stereogenic centers through a palladium-catalyzed desymmetric C-H bond imidoylation has been developed.α,α-Diaryl tri-and difluoroethylated isocyanides were used as powerful precursors of chiral 1H-isoindoles,in which the fluoroalkyl group was proven to play a crucial role in both the stereochemistry and reaction efficiency.In addition,an allene insertion cascade was realized,offering rapid access to diverse Cl-tethered bis-heterocyclic scaffolds with good yields and high enantioselectivities.The reactions proceeded smoothly under mild conditions with low catalyst loadings.