Rapid Synthesis Of Azepinoindole Derivatives From Tryptamine Sulfonamides And Bromoallyl Sulfones Via An Acid-Mediated Cyclization And Rearrangement

The azepinoindole framework present in natural alkaloids such as subincanadine F, ibogaine and catharanthine was formed in a novel acid-promoted cyclization-rearrangement of tryptamine-derived N-sulfonyl enamines. The latter were conveniently prepared via a cesium carbonate mediated formal vinylic substitution reaction of 2-bromoallyl sulfones (allenyl sulfone surrogate) and tryptamine sulfonamides. The azepinoindole forming cyclization-rearrangement involves the initial generation of a six-membered tetrahydro-beta-carboline derivative. The steric bulk of the N-sulfonyl group on tryptamine plays an important role in deciding the reaction outcome.