Highly Efficient Indenyl-Phosphine Ligand:Synthesis And Application On C-C Coupling Reaction

C-C bonds are most important backbones widely existed in a number of natural products,pharmaceuticals,agricultural pharmaceuticals,and various organic functional materials.Due to the disadvantages to synthetize C-C bonds by traditional methods(SN reaction,nucleophilic addition and rearrangement reaction etc.),including low yield,uncontrolled by-products,and harsh conditions,the development of novel and efficient methods for syntheses of C-C bonds have been desired.The transtion metal catalyzed Suzuki-Miyaura and Sonogashira coupling reactions are the most efficient and convenient measures to construct C(sp2)-C(sp2)bonds and C(sp2)-C(sp)bonds,and have been widely applied in industrial and academic.Since proposal of the concept of "green chemistry",displacing traditional organic solvent in organic synthesis by low-toxic and environmental friendly solvent has been a very challenging and important goal.During the last two decades,in consideration of cost,environmental benefits and safety,there has been increasing interest in the use of water as a solvent for many organic reactions.Date back to the first example reported the use of water in Pd-catalyzed Suzuki-Miyaura cross-coupling reactions,to date,a great progress by using aryl iodides and bromides or actived aryl chlorides as substracts was achieved in this lore.However,only a few examples have been reported concerning palladium-catalyzed coupling reactions of aryl and heteroaryl chlorides with aryl boronic acids in purely aqueous reaction media.Sterically hindered biaryl structures exist in various biologically natural products and pharmaceuticals,and they also serve as pivotal motifs for efficient ligands.Due to the sterically hindered substrates,tri-or tetra-ortho-substituted biaryls are hardly synthetized by traditional methods.Suzuki-Miyaura coupling reaction is the most efficient measure to construct biaryl.To our knowledge,the sythesis of sterically hindered biaryl structures by Suzuki-Miyaura coupling reaction needs high catalyst loading,high temperature,and long time.Thus,the sterically demanding Suzuki-Miyaura coupling reaction remains a challenge.Base on the above studies,we aim to design and synthetize two kinds of novel indenyl phosphine ligands(L1 and L2),and carry out studies on the Palladium-catalyzed Suzuki-Miyaura and Sonogashira coupling reaction in water of phosphine ligands L1,and the Palladium-catalyzed sterically demanding Suzuki-Miyaura coupling of phosphine ligands L2.The main contents are shown as following:[1]A water-soluble indenyl phosphine ligands L1 have been synthesised and characterized by 1H NMR,31P NMR,13C NMR and elemental analysis.The Pd(OAc)2/L1 catalyst system is efficient for the Suzuki-Miyaura coupling reaction of aryl and heteroaryl chlorides in water.And the Pd(CH3CN)2CI2/L1 catalyst system is efficient for the Sonogashira cross-coupling reaction of aryl chlorides in H2O/CH3CN,especially heteroaryl chlorides.[2]A highly active indenyl phosphine ligands L2 have been synthesised and characterized by 1H NMR,31P NMR,13C NMR and HRMS.The Pd(OAc)2/L2 catalyst system is efficient for sterically demanding Suzuki-Miyaura coupling aryl and heteroaryl chlorides with(hetero)aryl boronic acids.