Stereochemical and mechanistic studies on the formation of the 3-oxoindolizidine skeleton from ornithine derivatives

Abstract
The reaction sequence that converts Boc-L- or Boc-D-Orn(Z)-OH into 8-amino-3-oxoindolizidine-2-carboxylate derivatives has been examined, in order to determine the step during which partial racemization occurs. By using chiral derivatizating agents, it has been demonstrated that the temperature-dependent racemization takes place during the intramolecular reductive amination process, involved in the elaboration of the indolizidine ring by hydrogenation of the corresponding 4-keto diester derived from ornithine. It was shown from deuterium labelling experiments that this process proceeds through an equilibrium between imine–enamine intermediates which also accounts for the high stereoselectivity in the generation of the C-8a centre of the indolizidine skeleton.

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