Studies On Visible Light Induced Csp~2 Involved Cross-coupling Reactions

Csp² involved cross coupling reactions are common approaches to construct new chemical bonds.Through these approaches,functional groups or fragments could be introduced into the core skeletons of pharmaceuticals,natural products,functional materials to enhance their pharmaceutical activity,biological availability,or other functionalities.Traditional coupling reactions usually require prefunctionalized groups,such as pseudohalides,specific halides,and organometallic functional groups that are preinstalled into the substrates.High toxic,unstable at high temperature,difficult to abtained and directing group preinstalled into the substrates limit application of these strategy.As an eco-friendly strategy,organic photochemistry has been widely applied to construct the biological active pharmaceuticals and natural products.The activation of C-H and C-F bond are the hot-spot in organic synthesis,while the high dissociation energy and short bond length are the remarkably challenges in the construction of pharmaceuticals and natural products.Arenes,perfluoroarenes and gemdifluoroalkenes?without the directing groups?were selected as the model subtrates to investigate the activation process of C-H and C-F bond with the photoredox catalysis and explore the regioselctivity cross-coupling reactions between Csp²-Csp²?Csp²-Csp³ and Csp²-S,a series of biaryl moieties,perfluoroaryl ethers and monofluoroalkenes derivatives were obtained with these strategies.Directing cross-coupling dehydrogenative arylation between 2-naphthylamine/ 2-naphthol derivatives and diarylamines has been applied to construct nonsymmetrical atropisomeric biaryls by emplowing Ir?d FCF₃ppy?₂dtbpyPF₆ as the photocatalyst,ammonium peroxysulfate as the oxidant under the irradiation of visible-light.Further exploration of substrates demonstrated that the homo-coupling products,BINOL/BINAM type derivatives could be isolated from the reaction system.Stern-volmer quenching experiments and control experiments indicated the mechanism proceed with reductive quenching cycle through radical-radical coupling pathway.This synthetic method creatively broadened the substrates scope and prevented the reaction system from strong oxidant,high temperature and prefunctionalized the substrates.The cross-coupling reaction between perfluoroarenes and ethers occurred under the irradiation of visible light using quinuclidine as the hydrogen atom transfer?HAT?catalyst,Ir?dFppy?₂bpyPF₆ as the photocatalyst,providing a series of multifluoroarylation ethers and amines.Deuterium labeling experiment on this novel transformation revealed that the C-H cleavage process might be involved in the rate-determining step.Sternvolmer quenching experiments and control experiments indicated the radical/radical process was involved.This strategy provides a concise,simple and efficient process and prevent it from peroxide,high temperature and directing-group involved substrates.In the visible-light mediated defluorinative reductive cross-coupling reaction of gem-difluoroalkenes,thiols served as reductive quencher and thiolation agent by using Ir?dFCF₃ppy?₂dtbpyPF₆ as the photocatalyst,K₂CO₃ as the base.Preliminary mechanistic studies?control experiments,radical trapping experiments?demonstrate that the mechanism was a radial addition and elimination process.A variety of thiols and gemdifluoroalkenes could undergo this reaction to selectively provide C-S coupling products,further studies on the natural products?Diosgenin and Dehydrocholic Acid derivatives?demonstrated that this novel synthetic method showed to be potential application value.