The Application Of Di-/multi- Nucleophiles In Transition Metal Catalyzed Organic Synthesis

Aromatic amines are nitrogen-containing compounds that are very important in the fields of natural product chemistry,pharmaceutical synthetic chemistry,and pesticide chemistry.As a nucleophilic reagent in organic reactions,aromatic amines have great advantages in the construction of C-N bond coupling reactions.The Chan-Evans-Lam reaction using transition metal copper as the catalyst is a reaction between an arylboronic acid and an amine,a phenol or a thiol compound to form C-N/C-O/C-S bonds.The reaction has made great progress,however the research of the different nucleophiles in such reaction has not gained much attention.Based on Chan-Evans-Lam reaction,we carry out related research,the specific content contains three parts:?1?O-/m-/p-aminobenzamide compounds containing two nucleophilic positions,can react with aryl boronic acids selectivity under Chan-Evans-Lam system catalyzed by CuCl.The optimal condition is as fallows:CuCl?15 mol%?,Et₃N?50 mol%?,methanol as solvent,room temperature,reaction time 12 hours,the yield of the model reaction reached 90%.The reaction system cauld be applied in with various halogen-substituted arylboronic acids.Vinyl groups,cyano groups cauld also afford good yields.25 target products were obtained,with the yield between 30%and 90%.The program provides a simple and effective solution for the synthesis of pharmaceutical intermediates,and has a great application prospect.?2?Based on the previous research,the weak assisting effect of the carbonyl group in a molecule which might exist in the reaction was studied in depth.The reaction of arylborate esters with aniline under Chan-Evans-Lam reaction system was developed by using weak assistant effect.The control experiments proved the existence of assisting effect.The optimal conditions are as follows:CuCl?15mol%?/Cu?OAc?₂?20 mol%?,Et₃N?50 mol%?,methanol as solvent,room temperature,reaction time 12hours.The yield of the model reaction was 79%.The reaction condition has good applicability and provide a simple and efficient experimental strategy for the application of arylboronate esters in Chan-Evans-Lam coupling reaction.?3?One-pot reactions to construct small molecules containing nitrogen heterocycles are simple and effective modular synthetic strategies.Referring to the previous work,a one-pot strategies for the preparation of N,N'-Diarylindazol-3-one compounds by copper-catalyzed C-N cross-coupling and dehydrogenation N-N bond formation was established.The optimal conditions are as follows,the first step:CuCl?20 mol%?,Et₃N?50 mol%?,methanol as solvent,room temperature,12 hours.The second step:120°C,dimethyl sulfoxide as a solvent,4 hours,the yield of the model reaction reached 94%.Moreover,the reaction system is suitable for various electrons and electron-deficient arylboronic acids,with good yields.This method combine perfectly with the previous reaction,and finally establishes a three-step one-pot reaction for the preparation of N,N'-Diarylindazol-3-one.