| Diversity-oriented synthesis(DOS)is an effective strategy for structurally diverse molecules construction from simple starting materials,which has been widely used in the synthesis of biologically active N-heterocycles.Fluorophores with aggregation-induce emission(AIE)properties exhibit broad applications in the organic light-emitting diodes,biological imaging,and chemical sensors,due to their strong fluorescence in aggregation and non-emission in solution.Therefore,it is of great significance to build new diverse AIE molecules with potential applications through the DOS strategy.The pyrrole[1,2]-fused heterocycles are the core scaffolds of many natural products,biologically active molecules and luminogens.Herein,we designed several new N-substituted pyrrole synthons with highly versatile reactive cites and novel reaction possibilities for DOS strategy,and they could simply,quickly and efficiently transform to diverse pyrrole[1,2]-fused scaffolds through intra-or inter-molecular reactions.Among them,new AIE molecules with large Stokes shift,full-color emission and high quantum yield were developed as specific fluorescent probes for cells and organelles imaging.The work was divided into the three following parts:Part I:The intramolecular nucleophilic aromatic substitution of hydrogen(S_NAr~H)reactions of single N-cyanomethylpyrrole realized pyrrolo[1,2-b]isoquinolinone derivatives construction as novel AIE molecules.The simple,fast,inexpensive and environment-friendly S_NAr~H reaction was limited to the nitrobenzenes.Therefore,novel N-cyanomethylpyrroles were designed for the direct transition-metal free intramolecular non-nitro group-assisted S_NAr~H C(sp~2)–H functionalization in the presence of base.These reactions provided three series of pyrrolo[1,2-b]isoquinolinone derivatives with good AIE properties.Meanwhile,changing the reaction solvent and base resulted in a set of unexpected rearrangement products 3-(1H-pyrrol-2-yl)-1H-inden-1-ones with red-emission which is ascribed to the donor-π-acceptor(D-π-A)structure.Reaction mechanism studies indicated that theσ~H adduct from carbanion addition to hydrogen(S_NAr~H)serves as the sole intermediate for all the aforementioned transformations.The subsequent Suzuki coupling reaction successfully incorporated triphenylamine moiety to pyrrolo[1,2-b]isoquinolinone derivatives and provided novel AIE molecules with red-shifted emission,large Stokes shifts and good quantum yields.Further living cell imaging investigations suggested their potential application as specific bioprobes for lipid droplets(LDs)localization and visualization.Part II:The intermolecular cascade reactions of double N-cyanomethylpyrroles gave highly-fused 4,6,11-trisubstituted pyrrolo[1’,2’:4,5]pyrazino[2,3-f]indolizine(5-6-6-5)scaffolds,and their aza-derivatives showed good AIE properties.The N-cyanomethylpyrroles were employed to construct conjugated six-membered bicyclic structure(6-6)through a[4+2]cycloaddition cascade reaction in one step.In this reaction,the two cyanomethyl fragments have different functions.These fasttransformations have the advantages of simple substrates with good adaptability as well as atom-economic property.The aza-derivatives imidazo[1’,2’:1,6]pyrido[3,4-e]imidazo[1,2-a]pyrazine showed good fluorescence and an additional methyl group was introduced to the ortho-nitrogen of 4-phenyl which led to novel AIE molecules by restriction the rotation of the"rotor".These molecules were then found to specifically target lipid droplets or mitochondria in the fluorescence imaging experiments.Part III:The intermolecular regioselective cascade reactions between two different N-acylethylpyrroles provided 5,6-disubstituted pyrrolo[1’,2’:1,6]pyrazino[2,3-g]indolizine(5-6-6-5)derivatives with AIE properties.The conjugated six-membered bicyclic structure(6-6)was constructed between 2-aldehyde and 2-cyano N-acylethylpyrroles through intermolecular regioselective cascade reaction in one step.These reactions featured easily available starting materials,broad substrate scope as well as economical in atom.Additionally,we proposed a possible mechanism for the regioselectivity based on the results of controlled experiments and mechanism research.The structure-fluorescence property relationship of the pyrrolo[1’,2’:1,6]pyrazino[2,3-g]indolizine(5-6-6-5)derivatives and their applications in cell imaging were also studied.In addition,based on the DOS study of carboxyl-directed transition metals catalyzed C–H activation,rhodium-catalyzed single/double C(sp~2)-H bond amidation cascade cyclization reactions were hence developped to construct 2-substituted/2,5-disubstituted benzoxazinone derivatives with AIE properties and excited-state intramolecular proton transfer(ESIPT)phenomenon.These reactions featured easily available starting materials,broad substrate scope as well as economical in atom.The rhodium-catalyzed C–H bond activation mechanism was also studied and proposed.In summary,based on the DOS strategy,we have designed,synthesized and discovered several novel AIE molecules with diverse core structures which were successfully applied in cells and specific organelles imaging.The above results indicate that the synthesis-structure-function chain research based on rational design could be the effective approach to find novel AIE probes. |
