Study On Silver-mediated [4+2] Annulation Reactions Of N-centred Radicals

Free radical reactions constitute a basic type of organic reaction and play an important role in organic synthesis.The initiation of N-centred radicals and the synthetic application of their rections are still challenging tasks in comparison with the extensive studies and wide application of carbon-centered radicals in organic chemistry.The dissertation deals with the annulation reactions of N-centred radicals with indoles and olefins,which have been applied to the synthesis of two structurally important heterocycles.Ag^?-mediated dearomative[4+2]annulation reactions of substituted indoles have been developed.In the air atmosphere,N-methoxyamides were used as the substrates to excite the N-centred radicals in the presence of AgOPiv,and then annulation with indoles to give pyrimidodiindol ketone derivatives.A series of control experiments,electrochemical experiments and DFT calculation have been conducted to dicuss the possible mechanism,indicating that the reaction underwent a“N-centred radical-carboncation”pathway.Various functional groups were well tolerated in the reactions.It is particularly worth mentioning that substrates such as tryptophan,typamine and indolleacetic acid derivatives,which have natural product fragments,could also afford target products in high yield.Meanwhile,the silver-mediated annulation reactions of olefins and N-centred radicals have also been developed.The N-methoxyamides bearing a variety of functionalgroupscouldsmoothlyreactwitholefinstoobtain dihydropyrimidoindolone derivatives in medium to excellent yields.The protocol featured the high atomic economy,easy to handle nature and good regioselectivity.The possible mechanism was verified by radical quchenching experiments,radical clock experiment,kinetic isotope effect?KIE?experiments and electrochemical experiments.The N-O bond in the target products could be cut off by SmI₂,which provides a new strategy for the synthesis of 5HT3 receptor antagonist analogues.The structures of all the synthetic compounds were confirmed by ¹H NMR,¹³C NMR and HRMS.The structures of target compounds have been confirmed by the X-ray single crystal diffraction analysis of compounds 3aa and 3af.