Stereoselective synthesis of 3,3′-pyrrolidinyl-spirooxindoles via the Zn(OAc)2-mediated asymmetric Mannich-type reaction

[Display omitted] •Zn(OAc)2 induces L-2-oxotryptophan to spirocyclize with aldehyde stereoselectively.•The stereoselective spirocyclization works for both aromatic and aliphatic aldehyde.•The stereochemistry of all four possible diastereomeric spirocycles is established.•The stereoselectivity is well explained with a zinc-chelated transition state. Zn(OAc)2-mediated Mannich-type reaction was studied for the synthesis of 3,3′-pyrrolidinyl-spirooxindole from l-2,3-dihydro-2-oxotryptophan methyl ester and aldehydes. The study indicates that the Mannich-type spirocyclization is significantly influenced by both the cation and anion of the metal salt, base, stoichiometry, stereoelectronics of aldehyde and temperature. With the enhancement by Zn(OAc)2, the substrate induced asymmetric reaction works on both aromatic and aliphatic aldehydes but at different temperatures. It could deliver the (2′S,3R,5‘S)-pyrrodinyl-spirooxindole with up to 96% of diastereomeric ratio in good yield under optimized conditions.