Organocatalytic Enantioselective Cascade Aza-Michael/Michael Addition Sequence for Asymmetric Synthesis of Chiral Spiro[pyrrolidine-3,3'-oxindole]s

The spiro[pyrrolidine-3,3'-oxindole] scaffold is common to a range of bioactive compounds; however, the asymmetric synthesis of this scaffold is complicated due to the presence of multiple chiral centers. An organocatalytic asymmetric cascade aza-Michael/Michael addition between tosylaminomethyl enones or enoates and 3-ylideneoxindoles catalyzed by a chiral squaramide that afforded complex and flexible spiro[pyrrolidine-3,3'-oxindole]s has been developed. Single-step construction of molecules with three contiguous stereocenters including one quaternary center in excellent yields with highly diastereo- and enantioselectivity are rare and should be useful in medicinal chemistry and diversity oriented synthesis of this intriguing class of compounds.