jo200896y_si_002.cif (18.63 kB)

3-(Hetero)aryl-4-indolylamino-α-tetralones by Diastereoselective Internal Redox Cyclization: An “Azaenamine” Conjugate Addition

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posted on 01.07.2011, 00:00 by Nugzar Ghavtadze, Rishikesh Narayan, Birgit Wibbeling, Ernst-Ulrich Würthwein
(E)-3-(Hetero)aryl-1-(2-((E)-(indolin-1-ylimino)methyl)phenyl)prop-2-en-1-ones 1 undergo 6-exo-trig cyclization reactions upon treatment with BF3·Me2S in dichloromethane at low temperature to give the tetralones 10 in good yield. This cyclization process can be considered to be an intramolecular Michael-type addition which is accompanied by an internal redox reaction as the indoline fragment is oxidized to indole with simultaneous hydrogen shift to nitrogen atom N1 and the α-carbon atom of the Michael system. The reactions at the iminic centers take place via umpolung of the classical carbonyl reactivity. The reaction is diastereoselective and affords exclusivly 3,4-disubstituted α-tetralones 10 as trans-diastereomers. According to quantum chemical calculations the reactions take place under kinetic control with the trans-diastereomer being the kinetically favored product as it has the lower activation barrier compared to the cis-diastereomer.