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. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)