.cui / L-proline Catalyzed Carbon-carbon Bond Coupling Reaction In The Indole Compounds And Drugs (+)-phenserine Key Precursor In The Synthesis Of Research

China Book Classification No.:O62One of the important methods for the formation of C-C bond is the Ullmann type reaction.The C-C bond coupling products are formed by the nucleophilic attack of the carbanion on aryl halides in the presence of the copper catalysts.However,for traditional Ullmann type reaction,harsh reaction conditions(high temperatures, strong bases,stoichiometric amounts of copper or copper salts,long reaction times) are needed to effect these transformations,usually only in moderate yields,leading to severe limitations in the generalizing this reaction,especially on a large scale.Since 10 years of studies on the Ullmann type reaction,our group had discovered 2 kinds of breakthrough:1.amino acids can be used as additives or ligands to induce acceleration of Ullmann-type reaction,making the reaction take place under very milder condition.2.when there exits an amide group next to the halide group on the benzene ring,this coupling reaction happens even at rt.So my dissertation was carried out around these two points.In the second chapter,we studied the C-C bond coupling reaction of 2-halotrifluoroacetanilides with active methylene compounds.We found that the reaction proceeded smoothly at rt,producing various C-C bond coupling products.At the end of this chapter,we speculated on the possible mechanism.This part of work paved the road for the following.We know,by far,only traces of synthesized organic compounds have bioactivities,while most of the bioactive compounds bear heterocycles.So,one of our targets is to synthesize these kinds of compounds.In the third chapter,we devised a way to the formation of 2,3-disubstituted indoles by the method described in the former chapter.Different 2,3-disubstituted indoles were produced by a cascade Ullmann C-C bond coupling/hydrolysis/condensation process.Besides,we invented another way to synthesize 2-trifluoromethylindoles in one-step catalyzed by CuI.For traditional methods to the formation of this kind of indoles,lots of drawbacks exists including inconvenient synthesis of the starting material,long steps,poor chemooselectivities as well as low yields.Using our method, 2-trifluoromethylindoles can be formed in one step in high yield.This part of work was introduced in the fourth chapter.In the fifth chapter,we applied the C-C bond coupling reaction catalyzed by CuI/L-Proline to the key ancestor of natural product,(+)-Phenserine,which is a drug for treating Alzheimer's disease.We ended up with the target molecule:oxindole aldehyde after 8 steps in 10.8%overall yields.