Azacyclic Carbene-catalyzed [3+3]aromatization To Synthesize 2-arylbenzothiazoles

Benzothiazole and its derivatives are widely existed in natural products.They have been used in bio-medicinal research,metal ion detection,and luminescent material development.The 2-position of the benzothiazole ring has frequently been modified to give various derivatives for biological and medicinal applications.For example:2-Arylbenzothiazole substituted compound 5F203 has anti-cancer effect;compound[¹¹C]PIB is used in clinical trials to diagnose early Alzheimer's disease;compound Phortress and GW610 have anti-tumor effect.In this thesis,?,?-disubstituted alkenal compounds were activated by NHC catalysts under oxidative conditions to react with enone substrates bearing benzothiazole fragments through LUMO activation strategies.?,?-Unsaturated acylazoliums were formed as the key intermediates in these transformations.2-Arylbenzothiazole derivatives were afforded as the final products in excellent yields.The product molecules obtained from our research were difficult to make through existed methodologies.This thesis mainly contains the following three chapters:(1)In Chapter 1,the development of NHC catalysis has been introduced.Specifically,remote activation reactions promoted by NHC catalysts in both non-chiral and enantioselective fashions have been described.(2)In Chapter 2,the significance of this project was discussed.For example,the practical applications of the benzothiazole groups in C-H activations and the traditional methods for the synthesis of functional molecules containing benzothiazole structures were introduced.(3)In Chapter 3,the detailed experimental studies on this project were described.An optimal reaction condition was established through examinations on the catalysts,oxidants,additives and solvents.The scopes of both reactants were also studied.Various 2-arylbenzothiazole derivatives were synthesized in good to excellent yields.The optimal reaction conditions are:Urazole(1.0 eq.),?-enal(2.5 eq.),K₃PO₄(200mol%)and DQ(300 mol%)in MTBE(1.5 m L)at 40?for 24 h.The desired products could be obtained in a high yield(72%).Synthetic applications of the corresponding2-arylbenzothiazole products were also investigated,with the benzothiazole moieties used as the directing groups in certain C-H activation reactions.Furthermore,the syntheses of corresponding NHC pre-catalysts and substrates were also included.