Iridium- and ruthenium-catalysed synthesis of 2,3-disubstituted indoles from anilines and vicinal diols

Matyas Tursky, Linda Luise Reeh Lorentz-Petersen, L. B. Olsen, Robert Madsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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*IrCl2](2)/MsOH or RuCl3 center dot xH(2)O/phosphine (phosphine = PPh3 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 alpha-hydroxyketone from the diol. The ketone subsequently reacts with aniline to generate the alpha-hydroxyimine which rearranges to the corresponding alpha-aminoketone. Acid-or metal-catalysed electrophilic ring-closure with the release of water then furnishes the indole product.
Original languageEnglish
JournalOrganic & Biomolecular Chemistry
Volume8
Issue number24
Pages (from-to)5576-5582
ISSN1477-0520
DOIs
Publication statusPublished - 2010

Cite this

Tursky, Matyas ; Lorentz-Petersen, Linda Luise Reeh ; Olsen, L. B. ; Madsen, Robert. / Iridium- and ruthenium-catalysed synthesis of 2,3-disubstituted indoles from anilines and vicinal diols. In: Organic & Biomolecular Chemistry. 2010 ; Vol. 8, No. 24. pp. 5576-5582.
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title = "Iridium- and ruthenium-catalysed synthesis of 2,3-disubstituted indoles from anilines and vicinal diols",
abstract = "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*IrCl2](2)/MsOH or RuCl3 center dot xH(2)O/phosphine (phosphine = PPh3 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 alpha-hydroxyketone from the diol. The ketone subsequently reacts with aniline to generate the alpha-hydroxyimine which rearranges to the corresponding alpha-aminoketone. Acid-or metal-catalysed electrophilic ring-closure with the release of water then furnishes the indole product.",
author = "Matyas Tursky and Lorentz-Petersen, {Linda Luise Reeh} and Olsen, {L. B.} and Robert Madsen",
year = "2010",
doi = "10.1039/c0ob00106f",
language = "English",
volume = "8",
pages = "5576--5582",
journal = "Organic & Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
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}

Iridium- and ruthenium-catalysed synthesis of 2,3-disubstituted indoles from anilines and vicinal diols. / Tursky, Matyas; Lorentz-Petersen, Linda Luise Reeh; Olsen, L. B.; Madsen, Robert.

In: Organic & Biomolecular Chemistry, Vol. 8, No. 24, 2010, p. 5576-5582.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Iridium- and ruthenium-catalysed synthesis of 2,3-disubstituted indoles from anilines and vicinal diols

AU - Tursky, Matyas

AU - Lorentz-Petersen, Linda Luise Reeh

AU - Olsen, L. B.

AU - Madsen, Robert

PY - 2010

Y1 - 2010

N2 - 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*IrCl2](2)/MsOH or RuCl3 center dot xH(2)O/phosphine (phosphine = PPh3 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 alpha-hydroxyketone from the diol. The ketone subsequently reacts with aniline to generate the alpha-hydroxyimine which rearranges to the corresponding alpha-aminoketone. Acid-or metal-catalysed electrophilic ring-closure with the release of water then furnishes the indole product.

AB - 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*IrCl2](2)/MsOH or RuCl3 center dot xH(2)O/phosphine (phosphine = PPh3 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 alpha-hydroxyketone from the diol. The ketone subsequently reacts with aniline to generate the alpha-hydroxyimine which rearranges to the corresponding alpha-aminoketone. Acid-or metal-catalysed electrophilic ring-closure with the release of water then furnishes the indole product.

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DO - 10.1039/c0ob00106f

M3 - Journal article

VL - 8

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JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

SN - 1477-0520

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