Vinylogous hydrazone activation in stereoselective synthesis of 2,3-dihydro-1H-pyrrolizines – an organocatalytic, metal-free route to ketorolac

In this paper, the application of organocatalysis in the synthesis of 2,3-dihydro-1H-pyrrolizines is demonstrated. α,β-Unsaturated aldehydes and pyrrole-based hydrazone readily participated in the formal (3+2)-cycloaddition that was realized according to aminocatalytic iminium ion activation. Products were obtained in high chemical yields, with excellent stereocontrol and selected additional transformations were also presented. The developed method was utilized in the first organocatalytic synthesis of ketorolac, a non-steroidal anti-inflammatory drug.