Iridium- and ruthenium-catalysed synthesis of 2,3-disubstituted indoles from anilines and vicinal diols.
A straightforward and atom-economical method is described for the synthesis of 2,3-disubstituted indoles. Anilines and 1,2-diols are condensed under neat conditions with catalytic amounts of either [Cp*IrCl(2)](2)/MsOH or RuCl(3)·xH(2)O/phosphine (phosphine = PPh(3) or xantphos). The reaction does not require any stoichiometric additives and only produces water and dihydrogen as byproducts. Anilines containing methyl, methoxy, chloro and fluoro substituents can participate in the cyclocondensation. Meta-substituted anilines give good regioselectivity for 6-substituted indoles, while unsymmetrical diols afford excellent regioselectivity for the indole isomer with an aryl or large alkyl group in the 2-position. The mechanism for the cyclocondensation presumably involves initial formation of the α-hydroxyketone from the diol. The ketone subsequently reacts with aniline to generate the α-hydroxyimine which rearranges to the corresponding α-aminoketone. Acid- or metal-catalysed electrophilic ring-closure with the release of water then furnishes the indole product.
Department of Chemistry, Building 201, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Matyas
M
Tursky
Linda L R
LL
Lorentz-Petersen
Lasse B
LB
Olsen
Robert
R
Madsen
D000438:Alcohols / Q000737:chemistry*; D000814:Aniline Compounds / Q000737:chemistry*; D002384:Catalysis; D007211:Indoles / Q000138:chemical synthesis*; D007495:Iridium / Q000737:chemistry*; D015394:Molecular Structure; D012428:Ruthenium / Q000737:chemistry*
D000438:Alcohols; D000814:Aniline Compounds; D007211:Indoles; D007495:Iridium; D012428:Ruthenium; C023650:aniline