Palladium-catalyzed Olefinic C-H Difluoromethylthiolation At Room Temperature

The emergence of SCF₂H-containing pharmaceuticals and agrochemicals has prompted researchers to develop effective methods for the construction of sulfur-containing difluoromethyl molecules.In the past few decades,significant progress has been made in the introduction of SCF₂H groups into organic molecules via nucleophilic,electrophilic,and radical pathways.Among these methods,the direct thiodifluoromethylation of C-H is a very attractive method to directly construct thiodifluoromethyl-containing molecules with high atom economy.So far,the thiodifluoromethylation of a series of target substrates C-H has been well developed.However,direct thiodifluoromethylation of alkene C-H is extremely rare.And the reported methods for synthesizing thiodifluoromethyl-substituted alkenes are limited to obtaining E isomer products.So far,no method for selectively forming Z-configuration thiodifluoromethylated alkene molecules has been reported.Transition metal catalysis is a powerful tool for selective C-H activation,offering the possibility to synthesize alkene molecules with single substitution configurations.In this paper,based on previous researches,a transition metal-catalyzed direct thiodifluoromethylation reaction system of olefin C(sp~2)-H was designed.The C-H functionalization strategy was adopted.8-Aminoquinoline as the directing group and Phth-SCF₂H as the sulfur difluoromethylation reagent,the first palladium-catalyzed C-H direct sulfur difluoromethylation of alkenes in air at room temperature was achieved in these mild reactions.A series of acrylamides were functionalized with high efficiency and showed good functional group tolerance.The subsequent success of the gram-level experiment,the further functional transformation of the product,and the smooth removal of the guiding group under different conditions further proved the synthetic utility of this method in obtaining high value-added sulfur difluoromethyl compounds.Mechanistic study experiments show that this method is an electrophilic,Z-selective C-H activation process.Two-dimensional NOE spectra and X-single crystal diffraction atomic lattice patterns more intuitively show that the reaction product is a single Z-substituted alkene molecule.This opens up a new avenue for constructing Z-SCF₂H-containing organic molecules with high selectivity and efficiency under mild conditions.