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News from the 80‐Year‐Old Passerini Variant of the Friedel–Crafts Alkylation of Indole
Author(s) -
Desimoni Giovanni,
Faita Giuseppe,
Mella Mariella,
Toscanini Marco,
Boiocchi Massimo
Publication year - 2008
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200800841
Subject(s) - chemistry , alkylation , trifluoromethanesulfonate , scandium , indole test , adduct , friedel–crafts reaction , catalysis , medicinal chemistry , crystal structure , stereochemistry , organic chemistry
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‐(1 H ‐indol‐3‐yl)acetates 4a – f . When the reactions are catalysed by 5 mol‐% scandium triflate (Sc III Tf), 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‐(1 H ‐indol‐3‐yl) acetates 5 are obtained, and their structures were confirmed by the X‐ray crystal structure analysis of 5a . Under milder conditions, Sc III Tf 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)