Multicomponent Reactions of Indole, Ethyl Glyoxylate and Anilines: From Friedel–Crafts to Aza‐Diels–Alder Reactions Catalysed by Scandium Triflate

The multicomponent reaction (MCR) of indole (1), ethyl glyoxylate (2) and 3,4‐dimethoxy‐ or 3,4‐methylenedioxyanilines (3a,b) give, in analogy to Friedel–Crafts alkylation of indole, expected acetates 4a,b. When the reactions are catalysed by scandium triflate, however, a completely different reaction pathway is followed and two pairs of diastereomeric aza‐Diels–Alder adducts (7a,b and 8a,b) are isolated, which result from the reactions in which the ethyl 2‐(arylimino)acetates (azomethynes of 2 with 3a,b) behave as heterodienes and indole is the dienophile. These products, whose structures were confirmed by X‐ray crystal structure analysis of 7a, are not derived from the scandium‐catalysed rearrangement of 4a,b, because when these latter are treated with Sc(OTf)3, the rearrangement produces acetates 5a,b only. The limits of the aza‐Diels–Alder reaction were investigated by performing the MCR on substituted anilines 3f–k. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) The multicomponent reaction of indole, ethyl glyoxylate and 3,4‐dimethoxy‐ or 3,4‐methylenedioxyanilines gives, in analogy to Friedel–Crafts alkylation of indole, expected products 4a,b. In the presence ofscandium triflate as a catalyst, the aza‐­Diels–Alder pathway is followed to give adducts 7a,b and 8a,b. The position of the methoxy groups is critical for the reaction pathway.