Design,Synthesis And Application Of Ferrocenylindene Skeleton Phoshine Ligands

The stable,easy-to-treat and easy-to-modify solid properties of ferrocene can usually be transferred to many of its derivatives,which has attracted the attention of many chemists.Especially in organic synthesis,the ligands and catalysts designed with these frameworks have achieved great success and have wide applicability in asymmetric conversion.Based on this,this paper conducts the following three parts of research.（1）Design and synthesis of phosphine ligandsFerrocenylindene was synthesized by intramolecular asymmetric C-H bond cyclization reaction and reduction of ferrocenylindene ketone.Seven ferrocenylindenes with different substituents were synthesized by introducing dimethylamine、morpholine、methoxy、phenyl、chlorine at position 7 and methoxy、methyl、and chlorine at position 6.Then,18 phosphine ligands were prepared by lithium-halogen exchange reaction at the indenyl ferrocene site,including 4 P-N ligands,3 P-O ligands and 11 monodentate phosphine ligands modified with steric and electrical properties.8 ferrocenylindenes and 18 phosphine ligands were characterized by NMR,HRMS,and HPLC.The absolute configuration of the ligand was determined by X-ray single crystal diffraction.The ligands were applied in the following two reactions.（2）Application of ligands in the C（sp2）-N Cross-Couplings of Secondary Amines with Aryl ChloridesUnder the conditions of（1%mol）Pd（OAc）₂,（2%mol）Ligand,Na OAc as base,reaction at 80°C for 20 h,the double-toothed phosphine Ligand based on ferrocene indene skeleton showed better catalytic performance than the single-toothed phosphine Ligand.When p-chlorotoluene and morpholine were used as substrates,the yield of P-N ligand P13,P-O ligand P11 and P12 was over 88%,and the yield of P-N ligand P13,P-O ligand P11 and P12 reached 99%.Under the same conditions,compared with the biaryl ligands,Dave Phos（93%）and SPhos（97%）exceeded,reaching the same catalytic ability as the famous ligand Ru Phos（99%）.Different electronic effects or ortho-substituted substrates and heterocyclic pyridine can complete the reaction well,the yield is between 80%-99%.The mechanism analysis shows that the rigid steric hindrance of ligand skeleton ferrocene indene and the electron-donating groups such as oxygen and nitrogen which can coordinate with metal at position 7 play an important role in the catalytic ability of ligand in this reaction.（3）Application of ligand in Lu’s[3+2]asymmetric cyclization reactionThe screening results of the designed and synthesized phosphine ligands in the reaction show that the steric hindrance of 6 and 7 sites of the ligand structure has an important influence on the enantioselectivity of the reaction.In the screening of substrates,it was found that the ligands only had good chiral induction ability to the substrates of acrylates,and the best result was that the monodentate ligand P1modified with a certain steric hindrance at 6 position had 80%ee value when methyl acrylate was used as the substrate.In addition,the mechanism analysis showed that P1 was the chiral induction of the product through the large steric hindrance rigid skeleton combined with planar chirality.