Atroposelective Synthesis Of Axially Chiral Biaryls And Styrenes Via Pd-Catalyzed Asymmetric C-H Activation Strategy

Axially chiral compounds are widespread in natural products,biologically active compounds,and useful chiral ligands in asymmetric catalysis.Because of the importance of this structural motif,the catalytic enantioselective construction of axially chiral scaffolds has been intensively investigated by chemists.In distinct contrast to the well investigated axially chiral biaryls,axially chiral styrenes,which exhibit a chiral axis between a substituted alkene and an aromatic ring have been largely overlooked,results in relatively lower barriers to rotation compared to their biaryl counterparts.Meanwhile,Pd-catalyzed enantioselective C-H bond activation has received much attention as an important tool for the expedient synthesis of chiral molecules.Base on this context,the dissertation mainly focused on atroposelective synthesis of axially chiral biaryls and axially chiral styrenes via Palladium-catalyzed asymmetric C-H functionalization strategy.The main details were listed as follows:1.Atroposelective Synthesis of Axially Chiral Biaryls via Pd(Ⅱ)-Catalyzed ThioetherDirected C-H Olefination and AllylationWe present herein our experimental and DFT computational studies on the directing ability of chalcogenoether motifs in Pd-catalyzed atroposelective C-H functionalization.Both Pdcatalyzed enantioselective C-H olefination and allylation reactions were successfully developed to synthesis of axially chiral biaryls.A broad range of axially chiral biaryls in good yields with excellent enantioselectivities were successfully accomplished via a Pd(Ⅱ)/chiral phosphoric acid catalytic system.This method could also be employed to access synthetically challenging atropisomers bearing two stereogenic axes with excellent enantioselectivities and diastereoselectivities.In addition,DFT calculation provided the convenience for reaction condition optimization and further enlighten the understanding of the reaction mechanism.2.Atroposelective Synthesis of Axially Chiral Styrenes via Pd(Ⅱ)-Catalyzed Aryl C-H Functionalization StrategyWe report herein the highly atroposelective synthesis of axially chiral styrenes with an openchained alkene via Pd(Ⅱ)-catalyzed C-H alkenylation and alkynylation using L-pyroglutamic acid as an inexpensive and catalytic chiral ligand.The potent application of the styrene atropisomers is demonstrated by a Co(Ⅲ)-catalyzed enantioselective C-H amidation of ferrocene using axially chiral styrene-type acid as chiral ligand.Experimental and computational studies were conducted to elucidate the reaction mechanism.Initial rate studies revealed a ligand deceleration effect(LDE)in this reaction.The chiral induction model of the enantioselectivity-determining C-H bond activation step was also provided based on DFT calculations.3.Atroposelective Synthesis of Conjugated Diene-Based Axially Chiral Styrenes via Pd(Ⅱ)-Catalyzed Thioether-Directed Alkenyl C-H OlefinationWe report the highly atroposelective synthesis of axially chiral styrenes with a conjugated 1,3-diene scaffold via Pd(Ⅱ)-catalyzed thioether-directed alkenyl C-H olefination strategy.This strategy features easy operation,mild reaction conditions,high functional group tolerance(69 examples),complete Z-selectivity,and excellent enantioselectivities(up to 99%ee).Notably,the highly enantioselective synthesis of atropisomers with two stereogenic axes were also achieved using this strategy.Moreover,the reaction could be scaled up and the resulting axially chiral styrenes could be easily oxidized into chiral sulfoxide derivatives with high diastereoselectivities,which showed great promise as a new type of sulfur-olefin ligand.