Palladium-and Cobalt-Catalyzed Regio-and Stereoselective C-H Functionalization

C-H activation is one of the most important strategies in organic synthesis.Owing to the high atom and step economies compared with traditional approaches,it has attracted tremendous attentions as a valuable tool for the synthesis and decoration of organic molecules.Particularly,transition metal catalyzed C-H activation via directing group strategy has emerged as a powerful method for overcoming the high strength of the C-H bond and realizing both precise regio-and stereoselective C-H activation.This methodology has revolutionized the field of organic chemistry in recent decades.This dissertation mainly focused on transition metal palladium-and cobalt-catalyzed regio-and stereoselective functionalization of inert C-H bonds assisted by directing group.The main content includes:1.Palladium-Catalyzed ortho-C–H Silylation of Biaryl Aldehydes Using a Transient Directing GroupWe present a strategy for Pd-catalyzed ortho-C–H silylation of biaryl aldehydes enabled by a transient auxiliary.This protocol provides a broad range of ortho-silylated biaryl aldehydes in good yields.Meanwhile,the silyl moiety can be further functionalized under mild conditions,rendering the silylated products useful building blocks.Notably,this protocol also offers an opportunity to establish a platform for expeditious synthesis of structurally diverse axially chiral biaryl aldehydes via sequential atroposelective interannular C–H functionalization/intraanular C–H silylation.2.Atroposelective Synthesis of N-Aryl Peptoid Atropisomers via a Palladium(II)-Catalyzed Asymmetric C–H Alkynylation StrategyWe report the efficient synthesis of a wide variety of N-aryl peptoid atropisomers in good yields with excellent enantioselectivities(up to 99%yield and 99%ee)by palladium-catalyzed asymmetric C–H alkynylation.The inexpensive and commercially available L-pyroglutamic acid was used as an efficient chiral ligand.The exceptional compatibility of the C–H alkynylation with various peptoid oligomers renders this procedure valuable for peptoid modifications.3.Cobalt-Catalyzed Atroposelective C-H Arylation of Biaryl-2-Amine Derivatives with Arylboronic AcidsWe develop a cobalt-catalyzed atroposelective C-H arylation strategy for the efficient synthesis of axially chiral biaryl-2-amine derivatives by using simple chiral salicyloxazoline ligand(Salox)and readily available arylboronic acids.Excellent yields and enantioselectivities were obtained(up to 99%yield and 99%ee).And the potential utility of this method is demonstrated in the gram-scale synthesis and further synthetic transformations.4.Cobalt-Catalyzed Asymmetric C(sp~2)-H Annulation of Benzylamine Derivatives with Alkynes:Synthesis of Chiral 1,2-DihydroisoquinolinesWe report an asymmetric C(sp~2)-H annulation of benzylamine derivatives with alkynes to synthesize chiral 1,2-dihydroisoquinolines via desymmetrization,parallel kinetic resolution,and kinetic resolution by combining a low-valent cobalt pre-catalyst with a readily-available chiral salicyloxazoline ligand(Salox).A wide range of enantiomerically enriched chiral 1,2-dihydroisoquinolines were obtained by this approach in good yields(up to 98%)with excellent enantioselectivity(up to>99%ee).And the potential utility of this method is demonstrated in the gram-scale,stereo-controlled formal synthesis of(+)-solifenacin,FR115427,(S)-cryptostyline II and(+)-NPS R-568.