Synthesis of iboga alkaloids by Pd-catalyzed heteroannulation of 2-iodoaniline with an internal alkyne as the key step

A convenient synthetic route to the iboga-scaffolds is described. Important steps include a Pd-catalyzed regiospecific indole formation between internal alkyne-substituted isoquinuclidine and 2-iodoaniline. The final cyclization was done using Trost’s Pd(II)–Ag(I) mixed-metal-mediated cyclization method originally developed for the synthesis of ibogamine. Both exo- (iboga) and endo-isomers (epi-iboga) at C-19 substitution with –CO2Me have been reported.