Studies On The Asymmetric Synthesis Of Oxindole Derivatives

Oxindole derivatives existed in numbers of natural and manual structures,different substitutes endowed oxindoles with various bioactivities,such as antitumor,antiviral,antiinflammation and antitubercular activities,means that oxindoles play an important role in the research of discovering new drugs,so that the synthesis of oxindole,particularly chiral oxindole,became more significant than others.Based on privious works,our group researched the asymmetric synthesis of oxindole under the catalysts of br(?)nsted acids.The details are followed:Firstly,the asymmetric 1,6-conjugate addition of phenols to para-quinone methides derived from isatins were developed,under the optimized condition,the substrate scope was completely examined,23 diphenyloloxindoles were synthesized with high yield(up to 99%)and excellent enantioselectivity(up to >99% ee).The absolute configuration was determined by X-ray crystal structure analysis and the ee value maintained in the further synthesis.Control experiments revealed that catalyst plays a vital role in the activation of reaction,and the existent of phenolic hydroxyl was also essential to the transformation.Then the reaction of thiols and 3-hydroxy-3-indolyloxindole was researched,in the presence of imidodiphosphoric acids,a series of oxindole derived ɑ-chiral thioethers were delivered.In the examination of the substrate scope,what surprised us was both aromatic and aliphatic thiols were amenable to this method.The substitutes in the substrates were completely evaluated,a total of 41 examples were developed with high yield(up to equivalent)and the ee value(up to >99%).Control experiments indicated that the NH group of indole motif is vital to the enantiocontrol.Under the catalysis of br(?)nsted acid,the ring opening reaction of thiols and 3-oxirane-indolin-2-ones was studied,under acid environment,thiols attacked the C3 position of 3-oxirane-indolin-2-ones,and the 3-thioindole was obtained.Then we evaluated the substrate scope of this approach,aromatic thiols bearing different substitutes were all compatible to the transformation,and benzyl thiols also afforded the desired product.Next examination of the oxindole demonstrated that the substitutes in the oxindole ring have negative affect to the reaction.25 examples were explored and delivered 3-thioindole with up to 83% yield.By the way the enantioselectivity of the product was also attempted.