A total synthesis of racemic and optically active ibogamine. Utilization and mechanism of a new silver ion assisted palladium catalyzed cyclization

Synthesis of Substituted 1‐Thiocyanatobutadienes and Their Application in a Diels—Alder/[3,3] Sigmatropic Rearrangement Tandem Reaction.

“…In the total synthesis reported by Trost et al this crucial C-C bond was formed using a palladium-catalysed Heck-type C-C coupling, in the presence of stoechiometric amounts of a silver salt [7]. The goal of our studies is to develop an alternative procedure for the synthesis of the strategic C-C bond avoiding use of stoechiometric quantities of a silver salt.…”

“…The isothiocyanate 3 can be easily transformed in three steps to the 2-azabicyclo[2.2.2]oct-5-ene 4 [5] (Scheme 1). This bicyclic compound has been used by Trost et al for the synthesis of desethylibogamine (5) [6,7].…”

“…Unfortunately, despite the encouraging results described by Lotsof [11] about treatment of opioid withdrawal with ibogaine (6b) on human patients, systematic clinical studies have not been carried out. Since the first total synthesis of 6a by B€ u uchi [12] in 1965, eleven other total synthesis have been reported [7,[13][14][15][16][17][18][19][20][21] but none of them is cost-and material-efficient enough to allow the production of this compound or of derivatives of this compound in large scale industrial production.…”

Synthesis of Substituted 1-Thiocyanatobutadienes and their Application in a Diels-Alder/[3,3] Sigmatropic Rearrangement Tandem Reaction

“…The isothiocyanate 3 can be easily transformed in three steps to the 2-azabicyclo[2.2.2]oct-5-ene 4 [5] (Scheme 1). This bicyclic compound has been used by Trost et al for the synthesis of desethylibogamine (5) [6,7].…”

“…Unfortunately, despite the encouraging results described by Lotsof [11] about treatment of opioid withdrawal with ibogaine (6b) on human patients, systematic clinical studies have not been carried out. Since the first total synthesis of 6a by B€ u uchi [12] in 1965, eleven other total synthesis have been reported [7,[13][14][15][16][17][18][19][20][21] but none of them is cost-and material-efficient enough to allow the production of this compound or of derivatives of this compound in large scale industrial production.…”