The stereoselective preparation of substituted pyrrolidines using titanium- and zirconium-mediated diene metallabicyclisation methodology: the total synthesis of (−)-α-kainic acid

Abstract

Zirconium- and titanium-mediated diene metallabicyclisation–elimination–functionalisation have been compared, contrasted and utilised for the preparation of 3,4-disubstituted and 2,3,4-trisubstituted pyrrolidines in high yield and excellent stereoselectivity. The zirconium-mediated methodology has been employed as the key step in a partial synthesis of (−)-α-kainic acid starting from D-serine, but the key metallabicyclisation sequence proceeded with poor stereocontrol. By contrast, the total synthesis of (−)-α-kainic acid starting from L-serine was accomplished using a titanium-mediated cyclisation sequence which proceeded with excellent stereocontrol. Novel kainoids and piperidines are also reported.