Construction Of Carbon-Fluorine Quaternary Stereogenic Center Via Palladium-catalyzed Allylic C-H Alkylation

Fluorinated chiral molecules are an important class of chiral compounds that are widely used in medicine,agriculture and materials science.The construction of fluorine-containing chiral compounds by asymmetric catalysis is difficult due to the special superconjugation effect and strong electronegativity of fluorine atoms,and the construction of fluorine-containing chiral quaternary carbon centers is a major challenge in synthetic chemistry.Among the methods for the construction of fluorinecontaining chiral quaternary carbon centers,asymmetric transition metal catalysis not only allows for a rich variety of reaction types,but also has many mature and efficient chiral control modes,and therefore has received increasing attention from chemists.We have designed the synthesis of ligand-containing fluorinated pre-chiral nucleophilic reagent α-fluoro-α-benzothiazole acetate to achieve chiral phosphoramide-palladium-catalyzed asymmetric alkylation of branched selective allyl carbon-hydrogen bonds for the efficient construction of α-fluoro-substituted esters with fluorinated chiral quaternary carbon centers,which can achieve up to 95%ee.During the screening of oxidants,it was found that the introduction of 2,5diphenylbenzoquinone could significantly improve the diastereoselectivity of the reaction.Mechanistic studies revealed that the 2,5-diphenylhydroquinone generated by the oxidative reduction of 2,5-diphenylbenzoquinone could influence the inner sphere bonding transition state of the allyl substitution process and thus the diastereoselectivity of the reaction through hydrogen bonding with nucleophilic reagents.This method enables the transition from simple materials to compounds with fluorinated chiral quaternary carbon centers and is applicable to a wide range of allylbenzenes.