Iridium-catalyzed condensation of amines and vicinal diols to substituted piperazines

Linda L R Lorentz-Petersen, Larsulrik R. Nordstroem, Robert Madsen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

A straightforward procedure is described for the synthesis of piperazines from amines and 1,2-diols. The heterocyclization is catalyzed by [Cp*IrCl 2] 2 and sodium hydrogen carbonate and can be achieved with either toluene or water as solvent. The transformation does not require any stoichiometric additives and only produces water as the byproduct. The reaction can be performed between a 1,2-diamine and a 1,2-diol or by a double condensation between a primary alkylamine and a 1,2-diol. At least one substituent is required on the piperazine ring to achieve the cyclization in good yield. The mechanism is believed to involve dehydrogenation of the 1,2-diol to the α-hydroxy aldehyde, which condenses with the amine to form the α-hydroxy imine. The latter rearranges to the corresponding α-amino carbonyl compound, which then reacts with another amine followed by reduction of the resulting imine. Piperazines are prepared by [Cp*IrCl 2] 2-catalyzed heterocyclization of 1,2-diols with either 1,2-diamines or primary alkylamines. The reaction is performed in toluene or water and requires no stoichiometric additive. The key step in the mechanism is believed to be the isomerization of an α-hydroxy imine to the corresponding α-amino carbonyl compound.

Original languageEnglish (US)
Pages (from-to)6752-6759
Number of pages8
JournalEuropean Journal of Organic Chemistry
Issue number34
DOIs
StatePublished - Dec 2012
Externally publishedYes

Fingerprint

Piperazines
Iridium
Imines
iridium
imines
Amines
Condensation
Carbonyl compounds
amines
carbonyl compounds
Diamines
condensation
Toluene
diamines
toluene
Water
water
Sodium Bicarbonate
Cyclization
Dehydrogenation

Keywords

  • Alcohols
  • Amination
  • Cyclization
  • Homogeneous catalysis
  • Nitrogen heterocycles

ASJC Scopus subject areas

  • Organic Chemistry
  • Physical and Theoretical Chemistry

Cite this

Iridium-catalyzed condensation of amines and vicinal diols to substituted piperazines. / Lorentz-Petersen, Linda L R; Nordstroem, Larsulrik R.; Madsen, Robert.

In: European Journal of Organic Chemistry, No. 34, 12.2012, p. 6752-6759.

Research output: Contribution to journalArticle

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AB - A straightforward procedure is described for the synthesis of piperazines from amines and 1,2-diols. The heterocyclization is catalyzed by [Cp*IrCl 2] 2 and sodium hydrogen carbonate and can be achieved with either toluene or water as solvent. The transformation does not require any stoichiometric additives and only produces water as the byproduct. The reaction can be performed between a 1,2-diamine and a 1,2-diol or by a double condensation between a primary alkylamine and a 1,2-diol. At least one substituent is required on the piperazine ring to achieve the cyclization in good yield. The mechanism is believed to involve dehydrogenation of the 1,2-diol to the α-hydroxy aldehyde, which condenses with the amine to form the α-hydroxy imine. The latter rearranges to the corresponding α-amino carbonyl compound, which then reacts with another amine followed by reduction of the resulting imine. Piperazines are prepared by [Cp*IrCl 2] 2-catalyzed heterocyclization of 1,2-diols with either 1,2-diamines or primary alkylamines. The reaction is performed in toluene or water and requires no stoichiometric additive. The key step in the mechanism is believed to be the isomerization of an α-hydroxy imine to the corresponding α-amino carbonyl compound.

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