Enantioselective Synthesis of CF ₃ -Containing 3,2’-Pyrrolidinyl Spirooxindoles and Dispirooxindoles via Thiourea-Catalyzed Domino Michael/Mannich [3+2] Cycloaddition Reactions

An efficient and practical organocatalytic asymmetric domino Michael/Mannich [3+2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines and arylidene azlactones by using a hydroquinine-derived thiourea as the catalyst has been disclosed. Under mild conditions, a broad range of CF ₃ -containing 3,2’-pyrrolidinyl spirooxindole/ dispirooxindole derivatives bearing four adjacent stereogenic centers including two vicinal spiro quaternary chiral centers were obtained in high yields (up to 99% yield) with excellent diastereoselectivities (>20:1 dr, in all case) and enantioselectivities (up to >99% ee). (Figure presented.).