Synthesis And Application Of Pyrazolidine Triazolidine Ligands

In this project,a class of new ligands similar to Bippyphos—pyrazolyl triazolylphosphine ligands,were designed using the bioppyphos as a template.Based on the synthetic route of Bippyphos,four synthetic routes were designed.The feasible synthetic route was selected by experiments,and two new ligands were successfully synthesized:5-dit-butylphosphine-1-(1'-ethyl-3',5'-diphenyl-1'H-pyrazole-4'-link)-1H-1,2,4-triazole(abbreviated as L5)and 5-diphosphine-1-(1'-ethyl-3',5'-diphenyl-1'H-pyrazole-4'-link)-1H-1,2,4-triazole(abbreviated as L6).The synthetic routes of the two ligands are as follows:Step 1:Dissolve Dibenzoylmethane in NMP,drop bromine at room temperature,after the reaction is finished,add water to precipitate solid and filter,then recrystallize with absolute ethyl alcohol to get?-bromobiphenylmethane.The purity of liquid phase was 98.5%and the yield was 94.42%;Step 2:Dissolve 1,2,4-Triazolylsodium in ultrapure solvent DMF,then add?-bromodibenzoyl methane dissolved in ultrapure solvent DMF dropwise at room temperature and heat up to 45°C after dropwise completion.After the reaction for 2-3 h,acetic acid was added,and then slowly dripping water with hydrazine.At the end of the reaction,the solids were precipitated with water and filtered to obtain 1-(3',5'-diphenyl-1'H-pyrazole-4'-link)-1H-1,2,4-triazole.The purity of liquid phase was 94.5%and the yield was 82.54%;Step 3:Dissolve the previous product in NMP,add potassium carbonate,add Iodoethane at room temperature.After the reaction is finished,add water to precipitate solid and filter,recrystallize with toluene,get 1-(1'-ethyl-3',5'-diphenyl-1'H-pyrazole-4'-linked)-1H-1,2,4-triazole.The purity of liquid phase was 98.7%and the yield was 96.56%;Step 4:Dissolve the previous product in the ultrapure solvent THF,drop the n-butyl lithium after cooling to-78°C,then slowly heat up to 0°C and hold for 1 hour.After cooling to-78°C again,drop the Di-tert-butylchlorophosphane or Dicyclohexylchlorophosphine,and then slowly return to room temperature after the drop is completed.after the reaction,the crude product was purified by column chromatography to obtain two ligands.The yield of L5 and L6 was 86.62%,79.39%and the purity was 97.7%and 96.7%respectively.Among them,the total yield of 5-dit-butylphosphine-1(1'-ethyl-3',5'-diphenyl-1'H-pyrazole-4'-combination)-1H-1,2,4-triazole(L5)was 65.18%;the total yield of 5-cyclohexyl-phosphine-(1'-ethyl-3',5'-diphenyl-1'H-pyrazole-4'-triazole)-1H-1-2,4-triazole(L6)was 59.74%.The products and intermediates were structurally characterized and analyzed by LC-MS,~1H NMR,single crystal diffraction,etc.Two newly synthesized ligands were applied to the Buchwald-Hartwig coupling reaction.The reaction conditions such as base?solvent?catalyst?temperature and so on were screened and the amount of catalyst and ligand,amine was optimized,and the substrate amines,halides and so on were extended.