Synthesis Of Tertiary Phosphine Based On P-Directed Ruthenium-Catalyzed Meta-C-H Bond Activation

In recent decades,the activation of arene C-H bond catalyzed by transition metal(TM)has attracted widespread attention as a replacement strategy for traditional cross coupling.The activation reaction of ortho-and para-C-H bonds has achieved relatively mature development;The activation reaction process of the meta-C-H bond is relatively complex,and research is still in its infancy.Therefore,improving the meta-selectivity of arenes has important research significance.The non-directed strategy is realized by direct activation of the meta-C-H bond of aromatic hydrocarbons.The step is highly economical,but the regioselectivity is poor,and the mixture is usually obtained.The directing strategy is to install a directing group(DG)containing N,O and S atoms,which can control the regioselectivity and directionally activate the meta-C-H bond of arenes.So far,transition metal catalyzed meta-C-H activation of arene has rarely used DG containing P atoms,so exploring the activation reaction of P-atom directed meta-C-H bonds in arenes is of great research significance.However,the electronegativity of P atom is lower,and the energy of the coordinate bond between P atom and transition metal as a DG is high,which is difficult to dissociate,leading to metal catalyst poisoning and loss of catalytic activity.In this paper,the strategy of introducing ligands is proposed to increase the steric hindrance,weaken the strong coordination between P atoms and transition metals,and inhibit the metal catalyst poisoning,to realize the meta-tertiary alkylation and difluoroalkylation of arenes.The main content is as follows:1.P-directed ruthenium-catalyzed tertiary alkylation of arenesIn this paper,we utilize a bicarbonyl ligand(1-cyclopropyl-1,3-butanedione)to achieve P-atom directed ruthenium-catalyzed meta-tertiary alkylation of arenes.Various substituted biarylphosphines and brominated alkylation reagents are resistant,with high yields and excellent regioselectivity.Mechanism studies have shown that P-atom not only assist in C-H metallization,but also activate remote σ-bood by inducing the formation of P-Ru-C bond.A series of meta-tertiary alkyl substituted phosphine compounds have been efficiently synthesized,providing a new strategy for supplementing the phosphine ligand library.2.P-directed ruthenium-catalyzed difluoroalkylation of arenesUsing a bicarbonyl ligand(2-acetylcyclohexanone)to achieve the P-atom directed ruthenium-catalyzed meta-difluoroalkylation of arenes.The substrate has good universality,high yields and excellent regioselectivity.Compared with the traditional fluorine atom introduction method,this strategy has higher step and atom economy.A series of fluorinated biphenylphosphine compounds with multiple functional groups were synthesized through gram scale reactions,hydrolysis,reduction reactions,and ortho-alkylation and arylation series reactions,enriching the library of organic phosphine ligands.