Catalytic Asymmetric Sequential Mannich/Molecular Cyclization To Construct Chiral Spiro [Pyrrolidine-3,3-oxindoles] Compounds

Chiral spiro[pyrrolidine-3,3-oxindoles]compounds is widely exist in the natural products with medicinal value and biological activities,such natural products most come from the plant.There is a little content in plants and can’t meet the needs of society.Therefore,synthesis of such compounds that using chemical method is becoming a hot research topic for chemists.In this paper,we using catalytic asymmetric one-pot sequential Mannich/Molecular cyclization to construct chiral spiro[pyrrolidine-3,3-oxindoles]compounds on the basis of predecessors.This method can be applied to total synthesis of natural products which contain chiral spiro indole ketone skeleton.The first part of the article introduced the research progress of Mannich reaction and the building of chiral spiro indole ketone.Mainly from the type of catalyst and the kinds of screw ring.In the second part of this paper,introduces the topic of design ideas and research methods and conclusions:we expound that organocatalytic asymmetric mannich reaction of C3-substituted oxindole with N-Boc protection of acetylene imine by chiral bifunctional tertiary-thiourea amine catalysts.Then happened moleculer cyclization under the iodine and inorganic base.One-pot to construct Chiral spiro[pyrrolidine-3,3-oxindoles]compounds.Select the best conditions:We used the toluence as solvent and 0.1 eq chiral quinine thiourea catalyst and reaction of 72h at the 75℃.Change of solvent for CH3CN,3eq I2 and leq K2CO3,shading,reaction of 2h at-20℃,got close 1 ring products with average rate of total yield(77%)and high enantioselectivity(up to 91%ee).When change of solvent for methylene chloride(DCM),4eq I2 and 2eq K3PO4·3H2O reaction of 24h at 40℃,got close 2 ring products with average rate of total yield(65%)and high enantioselectivity(up to 91%ee).We had a wide substrate scope including the substituent for electronics and electronic absorption and they have a highly versatile.