Enantioselective Synthesis Of Axial Chiral Biaryls By Pd-catalyzed Asymmetric C–H Functionalization

As a kind of chiral molecules with potential biological activity and catalytic functions,axial chiral biaryls have been widely applied to the modern medicine and organic chemistry.In recent years,significant progress has been devoted to the synthesis and application of such molecules.However,it is still a challenge to further research in this field,and also a tireless pursuit for chemists to construct biaryl atropisomers via a simple,efficient method.As a very convenient and efficient strategy,transition metal catalyzed asymmetric C–H activation has been widely employed for the synthesis of natural products and pharmaceutical active molecules.In this paper,we focus on the construction of biaryl atropisomers via transition metal catalyzed asymmetric C–H bond activation based on chiral tert-leucine and its derivative as catalytic transient auxiliary.1.Merging C–H and C–C activation in Pd-catalyzed enantioselective synthesis of biaryl atropisomersWe have developed a Pd(?)-catalyzed asymmetric C–H/C–C activation strategy for the synthesis of various biaryl atropisomers using chiral tert-leucine and its derivative as catalytic transient auxiliary,and the strained cyclopropane motifs as coupling partners.This reaction features several advantages,including a wide range of substrates,highly enantiocontrol,and gram scale synthesis.This method provided a new way to synthesize diverse axial chiral motifs via merging asymmetric C–H functionalization and C–C bond cleavage into a reaction.2.Pd-catalyzed atroposelective C-H alkenylation access to pentatomic heteroaromaticsWe have realized a Pd(?)-catalyzed asymmetric C–H alkenylation to access atropisomeric species featuring in five-membered heterocycle using chiral tert-leucine as a transient auxiliary,acrylate and alkene as coupling partner.The reaction features as mild condition,broad substrate scope and gram scale synthesis.This strategy expands the method of synthesis of axial chiral pentatomic biaryls enabled by asymmetric C–H functionzation.