Research On Chiral Construction Of 3,3'-disubstituted Oxindole Derivatives With Potential Bioactivity

In this thesis,we have committed ourselves to reaearch the asymmetric synthesis of 3,3'-disubstituted oxindole derivatives with a stereocenter catalyzed by the chiral thiourea ligand.The addition of alcohols to isatin-derived N-Boc ketimines go under mild condition and the scope of substrates is quite wide.In addition,we have also carried out substrate extension studies to broaden the range of substrates,Which provided a new method and a new idea for the construction of chiral compounds with good potential biological activity.Oxidized indole structural units are widely present in natural products and many important drug molecules.The chiral 3,3'-disubstituted oxindole compounds have high biological activity and are of great value in the fields of anti-cancer,anti-oxidation and anti-HIV.Therefore,it is of great significance to construct 3,3'-disubstituted indole compounds with 3-position chiral centers.In view of this,we have constructed asymmetric addition of alcohols to isatin-derived N-Boc ketimines catalyzed by chiral thiourea ligand.The optimal reaction conditions and results(96%yield and 92%ee)were obtained by screening and optimizing the catalyst,solvent,additives and temperature.Substrate extension was subsequently carried out,with most of the products having more than 90%yield and ee values,extending the range of suitable substrates.In a word,a 3,3'-disubstituted oxindole derivative with one stereogenic center was obtained by catalytic addition reaction.