B(C₆F₅)₃-catalyzed C-H Functionalization Of Indole And Its Application In Polymer Synthesis

Indole,quinoline and their derivatives are very important heterocyclic compounds and they are widely present in natural products and medicines as the core molecular skeleton.The development of highly selective catalyst systems for their specific transformations has always been a research hotspot.In recent years,the selective functionalization(i.e.borylation or silylation)of indoles has attracted intense attention,which could greatly enrich the structural range of indoles and obtain more flexible molecular building blocks.So far,most of the catalyst systems have been based on transition metals,while high-efficiency metal-free catalyst systems need to be further developed.Due to the inevitable formation of indoline byproducts,extra efforts are typically required to achieve the enhanced catalyst turnover,such as adding hydrogen acceptors,additives,excess boron and silicon sources,completing the reaction at high temperatures.For the reduction of quinoline to synthesize tetrahydroquinoline,direct hydrogenation is one of the most straightforward methods.This reaction also heavily relies on transition metal catalysts,with the requirement of high pressures and/or elevated temperatures.In recent years,some studies have shown that reducing agents such as ammonia borane can replace the high-pressure hydrogen,but it is necessary to add excess reducing agent and increase the temperature to promote the reaction.These constraints will lead to low atomic economy of the reaction and produce a large number of by-products.The high-temperature and high-pressure reaction conditions will make the reaction operation process dangerous and lead to more energy being wasted,which is not in line with the concept of green chemistry.Therefore,it has still been a difficult problem which is worth being solved by researchers and with the development of efficient metal-free catalyst systems,we can overcome the above constraints and realize these reactions with high atom economy under mild conditions.In addition,the development of suitable organocatalyst systems for the construction or modification of polymers is a research hotspot in the field of polymer synthesis.Introducing new elementary reactions to the synthesis of polymer has been a long-standing topic of polymer science because it greatly expands the structure and property library of polymers.Without any additional additives and byproducts,C3-borylated indoles and transfer hydrogenated indolines have been simultaneously achieved by B(C₆F₅)₃-catalyzed disproportionation reaction of a broad range of indoles with catecholborane.This catalyst system has exhibited great potential in practical applications,with features easy scale-up under solvent-free conditions in a low catalyst loading of 0.1 mol%and long catalytic lifetime over ten sequential additions of starting materials.A combined mechanistic study,including isolation and characterization of key reaction intermediates,in situ NMR of the reaction,and analysis of detailed experimental data,has led to a possible reaction mechanism which illustrates pathways for the formation of both major products and byproducts.Understanding the reaction mechanism enables us to successfully suppress side reactions by choosing appropriate substrates and adjusting the amount of catecholborane needed.More importantly,by increasing the reaction temperature to120°C,we could achieve the convergent disproportionation reaction of indoles,in which indolines were continuously oxidized to indoles for the next disproportionation catalytic cycle.Near quantitative conversions and up to 98%yields of various C3-selective borylated indoles were achieved.The above-mentioned C-H borylation of indoles,as well as the previous research on C-H silylation of indoles,both need to heat the reaction at 120°C to continuously oxidize the indoline back to indole,which proceed with disproportionation reaction again for the next catalytic cycle,thus achieving up to 99%yield of C3-regioselective borylated(or silylated)products.In the next work,we reported a one-pot B(C₆F₅)₃-catalyzed strategy for simultaneous synthesis of C3-regioselective functionalization of indoles and complete reduction of quinolines.By sharing a quinolinium hydridoborate intermediate,the original determining steps with high energy barrier in both the convergent disproportionation of indole and reduction of quinoline could be circumvented.Therefore,the C3-borylated(or silylated)indoles and N-borylated tetrahydroquinolines could be simultaneously obtained in up to 98%yields at room temperature.Mechanistic studies suggested that both reactions would consume a product generated from the other reaction such that they can mutually promote each other,thus producing desirable products in a high atom-economy and low energy-cost manner.It is the first time that the concept of mutualism has been applied to organic synthetic chemistry,which would possibly inspire the development of more examples of mutualism in organic synthetic strategies with potential applications in the future.Next,we introduced of the silylation of indoles to polymer chemistry.On the one hand,a novel type of polymer with both indole skeleton and silicon atoms in the back-bone was constructed by the step-growth polymerization of B(C₆F₅)₃-catalyzed silylation of indoles.A series of monomers and model compounds were designed and synthesized.Linear poly(silyl indole)s with good solubility could be obtained by AA+BB and AB type polymerization.The polymerization of trisilane and bisindole lead to hyperbranched polymers that were partially dissolved in generally used organic solvents.The resultant polymers have been fully characterized by various methods such as NMR,FT-IR,GPC and TGA.Interestingly,these polymer backbones contain both indole donors and silicon acceptors,which can undergo intramolecular electron transfer and thus emit blue-violet fluorescence under UV lamp excitation.On the other hand,the reversible addition-fragmentation chain transfer(RAFT)polymerization of 1-(4-vinylbenzyl)-indole was performed,furnishing a series of polystyrenes containing indole side groups.With the catalysis of B(C₆F₅)₃,post-polymerization modification of the produced polymers could be achieved through the silylation of their indole side groups with different hydrosilanes.Analysis of the polymers by GPC and ¹H-NMR spectroscopy revealed that the C3-position of indole group at the polystyrene side chain was selectively silylated while the polymer backbone was maintained.The employment of the less sterically crowded Ph Me₂Si H or silanes containing tetraphenylethene(TPE)moiety as silane sources led to the production of polymers with 50%or 38%grafting ratio of silylated indole,respectively.Moreover,hydrosilane containing tetraphenylethene(TPE)-moiety would endow the resultant polymer with the aggregation-induced emission feature.