The intramolecular Diels–Alder reaction of tryptamine-derived Zincke aldehydes is a stepwise process

Abstract

Computational studies show that the base-mediated intramolecular Diels–Alder of tryptamine-derived Zincke aldehydes, used as a key step in the synthesis of the Strychnos alkaloids norfluorocurarine and strychnine, proceeds via a stepwise pathway. The experimentally determined importance of a potassium counterion in the base is explained by its ability to preorganize the Zincke aldehyde diene in an s-cis conformation suitable to bicyclization. Computation also supports the thermodynamic importance of the generation of a stable enolate in the final reaction step. The thermal cycloreversion reaction of the Diels–Alder products is also found to proceed in a stepwise manner.