Asymmetric Aza-Michael-Michael Cascade Reaction:Versatile And Efficient Approach For The Synthesis Of 3,3’-Pyrrolidinyl Spirooxindoles

The method of asymmetric catalysis has been widely used in the synthesis of a variety of chiral drugs and natural products.Nitrogen-containing heterocyclic and pyrrolidinyl spirooxindoles compounds are always the skeleton of many kinds of chiral drugs and natural products.More and more researchers focused on the field of how to construct these compounds by asymmetric cascade reaction.As one of the methods of asymmetric catalysis,the aza-michael-michael cascade reaction not only reduced the use of raw materials,but also made the steps of reaction more predigestion.This method has a distinct advantage in the construction of various nitrogen-containing heterocyclic compounds and pyrrolidinyl spirooxindoles compounds.We presented an efficient method for the synthesis of 3,3’-pyrrolidinyl spirooxindoles.In reaction,we used the methyleneindolinones with aminocrotonate as the substrates under the catalytic of thiourea catalyst which was based on tertiary amine for the first time.The compounds have three contiguous chiral centers and a quaternary carbon center.This reaction was completed underway of wild condition in 24 hours,and at the same time the compounds had a good yield and selectivity(90%yield,>20:1d.r.and 99%ee),it also had a widely range of application in substrates.We believed that this kind of methods can provide a new route in synthesis of chiral drugs and natural products.