| As significant active intermediates,N-centred radicals（NCRs）have attracted extensive attention in organic synthesis in recent years.It is efficient and convenient to construct functionalized N-containing heterocycles by N-radical reactions.At the same time,with the improvement of the research and application level of photocatalysts and the deepening of people’s understanding of the photoreaction mechanism,visible-light-induced photoredox catalysis has been developed rapidly and achieved remarkable results,which has become one of the most popular research fields.It not only provides a new path for the mild generation of N-radicals but also creates conditions for new reaction design and synthesis of nitrogen-containing heterocyclic based on N-radicals.There are many ways to generate N-radicals by visible light catalysis,but they mainly focus on the reductive cleavage of some chemical bonds,such as N-O bonds,N-S bonds,N-N bonds,and N-X（X=Cl,Br,I,etc.）bonds.N-radicals can also be generated indirectly through radical chain reactions involving C-N and N-N bonds.However,these methods have many disadvantages such as complex substrate preparation and cumbersome steps.Although it is not easy to generate N-radicals through direct oxidative cleavage of N-H bonds,it is still attractive because this strategy has a wide range of substrates,no need for pre-functionalization,and a high atom economy.Therefore,combined with the current research progress of visible photocatalysis oxidative cleavage of N-H bonds to produce N-radicals,this paper has carried out the research of visible-light-induced N-radicals cyclization of alkenyl Weinreb amide.First,based on the previous work of our research group and abundant literature investigation,we determined that the research direction is the cyclization of N-radicals of alkenyl Weinreb amide and designed the overall reaction.The preliminary experimental exploration and DFT theoretical calculation show that this experiment is conducive to the synthesis of isoindolinones and 3,4-dihydroisoquinoline-1（2H）-ones through the cyclization of N-radicals.Both of them are typical N-heterocyclic with great biological and pharmacological activities and widely exist in natural products and drug molecules.Then,we focused on the visible-light-induced N-radicals 5-exo cyclization of alkenyl Weinreb amide.The optimum reaction system consisting of organic dye catalyst4Cz IPN,inorganic base Cs2CO3,protonation reagent 3-methylbenzenethiol,and solvent DCE was determined by condition screening.The selective synthesis of 12isoindolinones,including aliphatic and aromatic ones,was successfully realized.The gram scale,sunlight catalysis,further transformation,and free radical cascade experiments have achieved ideal results.In addition,we proposed a reasonable reaction mechanism based on the experiments of fluorescence quenching,1H NMR,free radical capture,and free radical clock.Subsequently,we studied the visible-light-induced N-radicals 6-endo cyclization of alkenyl Weinreb amide and realized the construction of 21 kinds of3,4-dihydroisoquinoline-1（2H）-ones by using the optimized conditions of the 5-exo cyclization reaction,and finally put forward a reasonable reaction mechanism,too.It is worth mentioning that the 9 kinds of isoindolinones are the by-product of this reaction,which can be used as a powerful supplement to the substrates cope in the 5-exo cyclization reaction,which fully reflects the high atomic economy of this reaction itself.In this thesis,the alkenyl Weinreb amide containing N-H bond was deeply studied utilizing visible photocatalysis,and the synthesis methodology of N-radicals5-exo/6-endo cyclization to synthesize isoindolinones/3,4–dihydroisoquinoline-1（2H）-ones were established.This methodology provides a novel synthesis strategy for the above two kinds of N-heterocyclic and can provide technical support for the synthesis of potential military special drugs.The bright spot is that we can selectively synthesize the target product by controlling the substitution model of the double bond of substrates.The organic dye 4Cz IPN is used as the photocatalyst,without metal and external oxidant,the reaction time is short,conditions were mild and efficient,and the operability is strong. |
