Stereoselective Organocatalytic Construction of Spiro Oxindole Pyrrolidines Using Unsaturated α-Ketoesters and α-Ketoamides

We have investigated the stereoselective formation of spiro oxindole pyrrolidines via formal [3+2] cycloaddition of oxindole imines with ketoesters and ketoamides. Bifunctional squaramide organocatalyst was able to induce enantioselectivity of up to 60 % ee, increased to 72 % ee after re-crystallization, in the formation of spiro pyrrolidines with ketoesters. Interestingly, ketoamides provided alternative spiro oxindole pyrrole products in addition to the main product, which was formed via a different reaction pathway. Structures of spiro oxindole pyrrolidine as well as pyrrole products were confirmed by X-ray crystallographic analysis. Two new squaramide based catalysts were synthesized and tested. DFT calculation helped elucidate the reaction course.

Automated summary

The stereoselective formation of spiro oxindole pyrrolidines via formal [3+2] cycloaddition of oxindole imines with ketoesters and ketoamides was investigated, with bifunctional squaramide organocatalyst inducing enantioselectivity of up to 72% ee. Ketoamides provided alternative products, and the reaction pathway was elucidated with the help of DFT calculation.