First total synthesis of ent-gelsedine via a novel iodide-promoted allene N-acyliminium ion cyclization

The first total synthesis of the oxindole alkaloid gelsedine (1) starting f rom (S)-malic acid is described. The key step is:a novel iodide-promoted in tramolecular reaction of an allene with: an N-acyliminium ion intermediate which provided in a single step the bicyclic vinyl iodide 11. Other importa nt steps are the highly stereoselective Pd-catalyzed Heck cyclization of N- methylanilide 23a which led to the desired spiro-oxindole 24a, the fully re gioselective intramolecular oxymercuration of 25a to the desired cyclic eth er, and the remarkable oxindole N-demethylation of 29 via a radical mechani sm by using dibenzoyl peroxide. The total synthesis was concluded by the st ereoselective introduction of the ethyl group from the bis-Boc compound 41: followed by methoxylation of the oxindole nitrogen. This total. synthesis l eads to the unnatural (+)-enantiomer of gelsedine in 21 steps and 0.10% ove rall yield.