News from the 80‐Year‐Old Passerini Variant of the Friedel–Crafts Alkylation of Indole

The multi‐component Friedel–Crafts alkylation reaction between indole (1), ethyl glyoxylate (2) and anilines (3a–f) gives, in analogy to the protocol of the old Passerini reaction, the expected ethyl 2‐(arylamino)‐2‐(1H‐indol‐3‐yl)acetates 4a–f. When the reactions are catalysed by 5 mol‐% scandium triflate (ScIIITf), however, or when the isolated products 4 are treated under the same conditions, rearrangements involving the arylamino fragments of adducts 4 take place. When the para position of 4 is unsubstituted, ethyl 2‐(2‐aminoaryl)‐2‐(1H‐indol‐3‐yl) acetates 5 are obtained, and their structures were confirmed by the X‐ray crystal structure analysis of 5a. Under milder conditions, ScIIITf gives more complicated products, deriving from 1, 2 and 3 in the ratio of 2:2:1, and these converted into 5. An explanation of the pathway, by which the Passerini adducts 4, coordinated to scandium, undergo the rearrangements, is proposed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)