Total synthesis of (5R,6R,8R,9S)-(−)-5,9Z-indolizidine 221T using sulfinimine-derived N-sulfinyl β-amino ketones

Abstract

The first total asymmetric synthesis of the poison frog alkaloid (−)-221T, a 5,6,8-trisubstituted indolizidine is described. The key core piperidine ring was constructed via an acid catalyzed intramolecular cascade Mannich cyclization reaction of a N-sulfinyl syn-α-methyl β-amino ketone and crotonaldehyde. The β-amino ketone was prepared via the reaction of prochiral lithium Weinreb amide enolate with an enantiopure N-2,4,6-triisopropylphenylsulfinyl imine.