Nickel-Catalyzed Asymmetric Cross-Electrophile Dicarbofunctionalization Of Alkenes And Alkynes

In organic synthesis,transition metal-catalyzed dicarbofunctionalization of alkenes or alkynes is one of the most efficient methods for carbon-carbon bond formation,which plays a crucial role in the synthesis of natural products,pharmaceuticals,and other structurally complex molecules.In recent years,nickelcatalyzed cross-electrophile coupling reactions have attracted extensive attention from organic chemists due to the advantages including mild reaction conditions,good functional group compatibility,and high step economy.As the research in this domain advances,this strategy is further applied to the cross-electrophile dicarbonfunctionalization of alkenes and alkynes.This dissertation focuses on nickelcatalyzed asymmetric cross-electrophile dicarbofunctionalization of alkenes and alkynes as well as cross-electrophile defluorinative alkylation of α-trifluoromethyl styrenes.In Chapter 1,nickel-catalyzed asymmetric cross-electrophile aryl-allylation of unactivated alkenes has been developed.Starting from aryl iodides-tethered alkenes and allyl carbonates,a broad range of chiral indanes and benzofurans have been synthesized under mild conditions in high regio-,E/Z,and enantioselectivity under the catalysis of nickel/PyrOX with zinc as the reductant.The intramolecular migratory insertion of the olefinic unit into the nickel aryl species serves as the enantiodetermining step,while terminal selective reductive elimination of the π-allyl nickel species results in the formation of linear products.In Chapter 2,nickel-catalyzed three-component asymmetric cross-electrophile trans-aryl-benzylation of β-alkoxyl-substituted α-naphthyl propargylic alcohols with aryl iodides and benzyl chlorides has been achieved under the catalysis of nickel/pyrimidine-oxazoline with zinc as the reductant,providing a new method to prepare all-carbon tetrasubstituted axially chiral allylic alcohols in high regio-,E/Z,and enantioselectivity under mild conditions.Relying on the hydroxyl group as the functional handle,such structural motifs are successfully derivatized into diverse functional-group-rich axially chiral alkenes.The atroposelective oxidative addition of benzyl chlorides to the nickel intermediate is likely enantiodiscriminating for the reaction,whereas the directing effect of the hydroxyl group leads to the E-configuration of the coupling products.In Chapter 3,nickel/titanium-cocatalyzed cross-electrophile defluorinative alkylation of α-trifluoromethyl styrenes has been accomplished.Among various organofluorines,gem-difluoroalkenes are not only present as a characteristic structural unit in biologically active compounds but also act as important precursors for the synthesis of other fluorine-containing compounds.Various α-trifluoromethylstyrenes were successfully reacted with a variety of alkyl halides under the cooperative catalysis of nickel/titanium with zinc powder as the reductant,allowing for the efficient synthesis of gem-difluoroalkenes under mild conditions.In this reaction,halogen atom transfer between the titanium catalyst and alkyl halides enables the cleavage of the relatively inert C-Cl bond,while the nickel catalyst promotes the formation of the C-C bond andβ-F elimination.Relying on this methodology as the key step,a series of γ-amino-gemdifluoroalkenes have been synthesized.The studies of half maximal inhibitory concentration of γ-amino-gem-difluoroalkene confirmed their antagonistic activity against the dopamine DRD2 receptor,enabling these compounds to be potential pharmaceuticals for the treatment of mental diseases related to the dopamine DRD2 receptor.Enantioselective aryl-allylation of alkenes,atroposelective aryl-benzylation of alkynes,and defluorinative alkylation of α-trifluoromethyl styrenes have been accomplished through the strategy of cross-electrophile coupling.