Total synthesis of indole alkaloids: Part I. Asymmetric synthesis of (-)-ibogamine. Part II. An approach toward the synthesis of koumine

Part I. The preparation of (−)-ibogamine ( 1) in fourteen steps from benzoquinone and in 10% overall yield is a powerful illustration of the value of the asymmetric Diels-Alder reaction as a starting point in a multistep synthesis. All four cycloadducts, 70, 77, 84 and 96, obtained with the (S)-BINOL-TiCl₂ complex were found to have the same absolute configuration. Furthermore, they are in the same enantiomeric series that Mikami observed with 1,4-naphthoquinone using the same catalyst, lending confidence to future stereochemical predictions that may be made with this system.; Part II. Three different routes for the synthesis hexahydroisoquinoline 98 met obstacles which defeated our approach to of the koumine. The Diels-Alder reaction of cyclic 1-azadienes 102 and 108 was abandoned due to the lack of reactivity of the dienes. An anionic oxy-Cope rearrangement of the azabicyclo[2.2.2]octane system caused mainly decomposition of the starting materials. Finally, an intramolecular [2+2] photocycloaddition generated “crossed”, “straight” and hydroisoquinoline products in varing ratios, depending on the substituent pattern of the substrate, but this approach was not synthetically useful. The results from this last study may be valuable for predicting the regiochemical outcome of certain intramolecular photocycloadditions.