Studies On Synthesis Of Quinolines By Direct Condensation Of Alkynes And Secondary Amides Activated By Tf₂O And Chiral Thiourea Catalyzed Asymmetric 1,4-addition Reaction Of Nitromethane To ?,?-unsaturated Cyclic Ketones

Quinolines is an important building block in organic chemistry.It not only exists in many natural products and drug molecules with important physiological activity,but also has important applications in the fields of medicine and industrial chemistry.Most of the quinoline derivatives have antibacterial,bactericidal and antiviral activities,thus there has been a demand for the development of a method for the rapid synthesis of quinoline derivatives.N-? alkyl-substituted cyclic amines are important building blocks of many biologically active natural products and drug molecules.One of the most direct methods of synthesizing such nitrogen alpha-alkyl-substituted cyclic amines is the alkylation of secondary cyclic amides.The formation of asymmetrical all-carbon quaternary chiral centers through the formation of carbon-carbon bonds is an important challenge in organic synthesis.The quaternary all-carbon chiral centers are contained in the backbone of natural products and drugs such as several sesquiterpenes,valerane and the like.Nitroalkanes are a wide variety of widely used and the equivalent of stable carbon anions.Therefore,it is of great significance to to develop a method for the construction of a chiral quaternary all-carbon center in a single step by the asymmetric addition of nitroalkanes to cyclic enones through the catalyst of thiourea.This dissertation contains the following three partions working:1.Metal-free synthesis of quinolines by direct condensation of amides with alkynes:revelation of N-aryl nitrilium intermediates by 2D NMR techniques(Chapter 2)Based on the Tf2O/2-F-Pyr.activation system,a method for the direct condensation of secondary amides and terminal alkynes to give quinoline derivatives was developed.At the same time,we detected the N-arylnitrile nitrilium ions using 2D NMR technology,which is an active intermediate that was not detected by in situ infrared technology.On this basis,we proposed a possible mechanism,namely secondary amides was activated by Tf2O/2-F-Pyr.to generated the nitrilium ions intermediates,then the nitrilium ions were subjected to the action of alkyne nucleophilic addition,followed by experiencing intramolecular Friedel-Crafts reaction,quinoline derivatives were obtained.2.The study of alkylation of cyclic amides(Chapter 3)We conducted a preliminary study of cyclic secondary amides activated by Tf2O reacted with non-metal nucleophiles.Only when naphthol was used as a nucleophile,the corresponding a-naphthalene imine could be obtained in 22%yield.Nuclear magnetic resonance monitoring also showed that the five-membered cyclic secondary amide under the activation of the Tf2O/2-F-Pyr.would mainly exist as the intermediates of N-trifluoromethanesulfonylated butyrolactam,while the six-membered cyclic secondary amide was converted into the intermediate of N-trifluoromethanesulfonyl valerolactam and the intermediate of trifluoromethanesulfonyl enol in a ratio of 2.7:1,and the desired active intermediate of O-trifluoromethanesulfonylated butyrolactam did not form in the experiment.3.Chiral thiourea catalyzed asymmetric 1,4-addition of nitromethane to?,?-Unsaturated Cyclic Ketones(Chapter 4)Asymmetric Michael addition of nitromethane to carbonyl ?-substituted cyclic enones catalyzed by commercially available chiral thiourea,approach to the construction of a chiral quaternary all-carbon center without adding another solvents in one step.Cyclic enones substrates can tolerate functional groups such as alkenyl groups,ester groups,ether bonds,acetals,and have good ee values in this reation.