Radical Conversion Of Unsaturated Enoximes And Indoles Under Oxygen Conditions

Polycyclic compounds are widely presented in natural products,bioactive molecules,and organic functional materials.Oxime compounds are a kind of raw materials,which are common,easy to obtain and widely used.Unsaturated enoxime compounds contain two active reaction sites: oxime and alkene moiety.The selective construction of oxygen/nitrogen heterocyclic skeletons based on free radical reaction strategy using unsaturated enoxime compounds has great advantages.Therefore,the development of new and efficient free radical reactions for unsaturated enoximes has research significance.Indolones are important organic synthetic materials or intermediates,with wide applications in pharmaceuticals,fragrances,pesticides,dyes,functional materials,and other fields.The dearomatization reaction of indole compounds is one of the most direct and convenient methods for synthesizing indolone compounds.Traditional synthesis methods using transition metals such as copper and silver or organic oxidants such as benzoquinone,high iodine compounds,and peroxides have led to serious environmental problems and produced a large number of by-products.Therefore,the development of a mild,efficient,highly selective,and environmentally friendly catalytic system to achieve the free radical dearomatization reaction of indoles and construct indolone compounds has important research significance an d application value.This article focuses on the development of free radical reactions involving unsaturated enoximes and indoles.The paper mainly includes the following four aspects:(1)Recent advances in the cyclization of unsaturated enoximes based on radical reaction strategy are reviewed.And oxygen as an oxidant involved in indoles free radical of dearomatization reaction,functionalization reaction,cyclization reaction and other oxidants involved in indoles dearomatization reaction based on free radical strategy are reviewed.The mechanisms of these reactions are also described and discussed.(2)A copper-catalyzed hydroxyl amination reaction of unsaturated enoximes with oxygen was found to produce hydroxyl-substituted cyclic nitrones.The reaction was initiated by a nitrogen radical generated on the oxime side,and a hydroxyl radical was formed during the reaction.The obtained final compound further expanded the range of unsaturated enoxime cyclization products.This method is characterized by simple operation,using green oxygen as oxygen atom source and terminal oxidant,cheap copper salt as catalyst,low cost and environmentally friendly ethanol as solvent,wide substrate range and excellent functional group tolerance.(3)A general method for the synthesis of 4-oxobutyronitrile by copper-catalyzedγ,δ-unsaturated enoximes nitrogen migration cyanide oxidation was established.This method uses cheap copper powder as a catalyst and unsaturated enoxime as a raw material.Through the intramolecular 5-exo-trig cyclization of free radicals,oxygen oxidation C=C bond cleavage and C-N bond cleavage ring-opening process,a one-pot tandem transformation of oxime and olefin to carbonyl and nitrile groups was achieved.The mechanism study showed that superoxide radical and aldoxime intermediate were formed during the reaction.In the past,unsaturated oximes obtained cyclization products through cyclization.The unsaturated oximes in the reaction obtained open chain compound by cyclization and bond cleavage.(4)A photocatalytic oxidative dearomatization of 2-substituted indoles were developed to synthesize a series of high-value indolinone derivatives containing indole substituents.In the reaction,2-substituted indoles was used as the donor,and the catalytic amount of 2-bromo-4’-nitroacetophenone was used as the acceptor.2-Substituted indoles and 2-bromo-4’-nitroacetophenone can form an EDA complex in the solvent and undergo electron transfer under light.The catalytic acceptor is regenerated by aerobic oxidation.The indolinone intermediates formed i n the reaction can react with their own substrates or by adding other types of indole reagents,and they do not affect each other.This method provides a new strategy for the synthesis of indolinone derivatives.In summary,this paper developed the cyclization hydroxylation reaction of unsaturated oximes,cyclization reopening reaction of unsaturated oximes and indole dearomatization reaction,and realized the green synthesis of oxygen-containing compounds such as pyrrole nitrones,γ-ketonitrile derivatives and indolinones.These synthetic strategies use environmentally friendly oxygen as oxidant and oxygen source,and can be carried out at room temperature,which provides a new solution for the synthesis of oxygen-containing organic compounds.