Asymmetric Synthesis Of Spirocyclopentane Based On Oxindoles

Indole alkaloid,as an important medical skeleton widely existing in bioactive heterocycles and natural products,has a variety of biological activities,such as anticancer,anti-HIV,antimicrobial,antioxidant and so on.In addition,indole structure is also considered to be the main active component in several alkaloids such as reserpine and mitomycin C.Moreover,the molecular structures of well-known medicines such as sumatriptan,tadalafil,fluvastatin and rizatriptan are based on indole skeletons.Therefore,chemists have paid more and more attention to the synthesis and biological activity of indole-containing compounds in the past decade.However,in indole alkaloids,often because of their high toxicity or lack of activity,it is difficult to be directly used as clinical drugs,and often need structural modification and modification.At the same time,asymmetric synthesis,as one of the common methods to construct and modify skeletons in drug synthesis,has the characteristics of convenience and economy,and has great potential in the synthesis of bioactive compounds.On the other hand,In organic synthesis,carbon amphiphilic nuclear reagents are important components of organic synthesis,which are widely used in the construction of carbocyclic compounds.Among them,1,2-C amphiphilic reagents are rarely found and used as synthons,and there are only 2 cases according to the literature.Herein,we developed a[2+3]annulation of 2-（2-oxoindolin-3-yl）malononitrile with 2-nitroallylic acetates,where 2-（2-oxoindolin-3-yl）malononitrile served as a new type of 1,2-carbon bisnucleophile.Through the control of stereoselectivity,indole compounds with single spatial configuration were obtained.Remarkably,the annulation reaction exhibits exclusive chemo-and regioselectivity.A novelMichael addition/SN₂ mechanism was proposed to avoid the"anti-Baldwin"cyclization.This highly stereoselective strategy provides a facile synthetic route for a new series of spirocyclopentane oxindole derivatives containing three stereogenic centers.It not only provides a reference method for the synthesis of spiropentane oxindole needed for drugs,but also provides an idea for the structural modification of indole skeleton medicine.