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2 H ‐Pyrrole Derivatives from an Aza‐Nazarov Reaction Cascade Involving Indole as the Neutral Leaving Group
Author(s) -
Ghavtadze Nugzar,
Fröhlich Roland,
Würthwein ErnstUlrich
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.200800384
Subject(s) - chemistry , pyrrole , protonation , indole test , hydrazone , medicinal chemistry , leaving group , cascade reaction , solvent , stereochemistry , organic chemistry , catalysis , ion
Trifluoromethyl‐substituted N ‐indolinyl‐1‐aza‐1,4‐dien‐3‐ones 4 , which are accessible in good yields from indolinylimino esters 6 in a two‐step procedure, undergo a novel type of aza‐Nazarov cyclization if treated with strong acids to give the hitherto unknown 3‐hydroxy‐5 H ‐pyrrole derivatives 8a – p . The solvent‐free polyphosphoric acid/acyl anhydride system as the acidic reaction medium is especially efficient and requires only short reaction times. According to quantum chemical calculations the key step in the reaction cascade is the cleavage of the N–N bond of the hydrazone fragment of a protonated N ‐(indolin‐1‐yl)‐1‐aza‐1,4‐dien‐3‐one intermediate such as 10 . This intermediate releases 3 H ‐indole as an unusual, but very efficient neutral leaving group. Several 1‐aza‐1,4‐dien‐3‐ones 4 and some 3‐hydroxy‐5 H ‐pyrrole derivatives 8 were characterized by X‐ray diffraction.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)