Visible Light-Driven Nitrogen Radical-Mediated C-C Bond Cleavage/Functionalization

Author:Yu Xiao Ye

Supervisor:chen jia rong xiao wen jing howard alper


Degree Year:2019





Nitrogen radical chemistry represents an important branch in the field of organic synthesis and has always aroused considerable interest of scientific community.In recent years,the rapid development of visible light photocatalysis has provided mild and effective access to generation of nitrogen radicals in a controlled way under very mild conditions.And nitrogen radicals have been successfully applied for activation/functionalization of inert C(sp3)-H bonds.However,visible light driven nitrogen radical mediated C-C bond activation is hitherto less explored.In this dissertation,recent advances in this field were reviewed and visible light induced imine radical mediated C-C bond cleavage/functionalization was also investigated.The detailed research works are listed as follows:First,we applied oxime esters as imine radical precursors,enabling cleavage of C-C single bonds under the mild condition of visible light photocatalysis to develop an efficient radical addition cascade.This method leads to a rapid entry to various diversely substituted cyano-containing compounds.Based on the results of radical trapping experiments,luminescence-quenching experiments,light on/off experiments and quantum yield measuration and so on,a possible mechanism was proposed.Then,we further achieved the photocatalytic neophyl rearrangement and reduction of distal carbon radicals through imine radical mediated C-C bond cleavage by rational design of substrate and screen of photocatalytic system towards valuable α,β-unsaturated nitriles or β-functionalized saturated nitriles.It is worth mentioning that this reaction can be enlarged scale and even gram scale without erosion of the reaction efficiency.According to the previous works and corresponding literature report,a imine radical mediated C-C bond cleavage/neophyl rearrangement and reduction process was postulated.In addition,we have also developed copper-catalyzed three-component radical cross-coupling of oxime esters,styrenes and boronic acids.This reaction features broad substrate scope and a simple procedure,which offers new horizons for various 1,1-diarylmethane-containing alkylnitriles.By screening a series of condition,we finally selected commercial available Cu(CH3CN)4PF6 as a catalyst.Under the mild condition,the desired products can be obtained with moderate to good yields.According to radical trapping experiments,EPR experiments and related literature reports,a CuⅠCⅡ/CuⅢ-based catalytic cycle was proposed.In view of the importance of arylalkylmethane derivatives,We developed a dual visible light photoredox and nickel-catalyzed cross-coupling reaction of 2-arylaziridines and potassium benzyltrifluoroborates.This reaction proceeded very well under the mild condition to afford desired products in good yields with exclusive regioselectivity.Notably,this reaction was applied for a continuous flow process to greatly reduce the reaction time without erosion of reaction efficiency.The control experiments indicated the nickel catalyst and photocatalyst were all crucial to this cross-coupling reaction.Finally,based on our previous work of nitrogen radical chemistry,we developed a visible light photocatalytic N-radical-based intramolecular hydroamination of benzamides,furnishing the desired 3,4-dihydropyrazole derivatives in good yields.Importantly,the continuous flow reaction could significantly shorten the reaction time and give the excellent yields.The sunlight irradiation also showed the synthetic potential of this method.