Lewis acid-mediated synthesis of mono- and tris-indole adducts from chiral aziridines

Lewis acid-mediated regio- and stereoselective nucleophilic addition of 2- or 3-substituted indoles to non-activated aziridine-2-carboxaldehydes in dioxane afforded 2-(indol-3-ylhydroxymethyl)aziridines whose ring opening with various nucleophiles rendered multi-substituted tryptamine derivatives. The reaction of the same aziridine-2-carboxaldehyde with three moles of indole in dichloromethane yielded tris-indole adducts β-(3,3′-bisindolyl)methyl (BIM) tryptamines from sequential steps including nucleophilic addition to aldehyde, Michael type Friedel–Crafts alkylation of the mono-adduct followed by regio- and stereoselective ring-opening of the aziridine ring.