Palladium-Catalyzed C-H Difluoroalkylation Of Ketene Dithioacetals And Applications

CF₂-containing olefin compounds are a class of attractive organic compounds and are widely used in the development of new drugs.Many research groups are committed to the synthesis of CF₂-containing olefin compounds.At present,it can be divided into two main categories:firstly,the transition metal catalyzed Csp²-H difluoroalkylation;secondly,the fluorine radical addition reaction of alkynes.Among them,olefin C-H difluoroalkylation reaction catalyzed by transition metal is an effective method for synthesis of these compounds directly.At present,the transition metal catalyzed difluoroalkylation of olefins C-H has been greatly successful,and the difluoroalkyl substitution of various olefins has been achieved.However,starting from three substituted olefins,the difluoroalkylation to CF₂-containing tetra-substituted olefins is very rare.?-H ketene dithioacetals as a class of multi reaction sites,polarizing and three substituted olefins,has been a widely used organic synthesis intermediate.Therefore,It is important to achieve?-H ketene dithioacetals difluoroalkylation reaction.This paper focuses on the C-H difluoroalkylation reaction of?-H ketene dithioacetals catalyzed by palladium and its application,mainly consists of three parts:1.The palladium-catalyzed C-H difluoroalkylation of three substituted olefins was successfully realized with?-H ketene dithioacetals and bromodifluoroacetate derivatives,and a variety of CF₂-containing tetra-substituted olefins were successfully synthesized.Among them,form?-carbamoyl ketene dithioacetals,the gem-difluorosuccinimides was directly separated by the catalytic cross coupling and further cyclization.Here,we provide an effective way for these compounds with CF₂ fragments.2.Based on the uniqueness of ketene dithioacetals and free radical inhibition experiments,we speculate that the difluoroalkylation of the olefin may be different from the previous palladium catalyzed Heck type mechanism.The process is proposed to involve two single electron transfer processes accompanied by an alternative loop from palladium?0?to palladium?I?,likely due to unique structural properties of ketene dithioacetals with?,?-dialkylthiol substituents on the olefin double bond.3.Based on the CF₂-containing tetra-substituted olefins which we obtained has multiple reaction sites,we tried the further transformation research.We realized the synthesis of all carbon four substituted olefins containing two fluorine alkyl substituents,and we realized the conversion from acetyl to vinyl chloride.