A Mild, Efficient Synthesis of gem-Difluorodihydrouracils

Francesca Olimpieri, Santos Fustero, Alessandro Volonterio, Matteo Zanda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Carbodiimides react effectively with beta-aryl/alkyl-beta-hydroxy-alpha,alpha-difluorocarboxylic acids to afford a vast array of fully substituted gem-difluorodihydrouracils through a two step reaction sequence. In the first step, condensation between the two reactants leads in most cases to the formation of a mixture of the desired dihydrouracils and N-acylurea co-products. However, the latter could be easily recovered and efficiently converted into the target compounds. The sequence works well in very mild conditions (CH2Cl2, 20 degrees C) and the reaction resulted to be completely regioselective when asymmetric carbodiimides were used. When the N-acylurea derivatives are not sufficiently stable for isolation, the process could be done in a one-pot fashion leading to the direct formation of the desired dihydrouracils, although in lower yields.

Original languageEnglish
Pages (from-to)651-660
Number of pages10
JournalSynthesis
Issue number4
DOIs
Publication statusPublished - Feb 2010

Keywords

  • N-heterocycles
  • fluorine
  • dihydrouracils
  • carbodiimide
  • domino reaction
  • N-acylureas
  • alpha,beta-unsaturated carboxylic-acids
  • pot sequential synthesis
  • acyl migration
  • alkaline-hydrololysis
  • peptide synthesis
  • beta-lactams
  • derivatives
  • carbodiimides
  • 3-component

Cite this

Olimpieri, F., Fustero, S., Volonterio, A., & Zanda, M. (2010). A Mild, Efficient Synthesis of gem-Difluorodihydrouracils. Synthesis, (4), 651-660. https://doi.org/10.1055/s-0029-1218587

A Mild, Efficient Synthesis of gem-Difluorodihydrouracils. / Olimpieri, Francesca; Fustero, Santos; Volonterio, Alessandro; Zanda, Matteo.

In: Synthesis, No. 4, 02.2010, p. 651-660.

Research output: Contribution to journalArticle

Olimpieri, F, Fustero, S, Volonterio, A & Zanda, M 2010, 'A Mild, Efficient Synthesis of gem-Difluorodihydrouracils', Synthesis, no. 4, pp. 651-660. https://doi.org/10.1055/s-0029-1218587
Olimpieri F, Fustero S, Volonterio A, Zanda M. A Mild, Efficient Synthesis of gem-Difluorodihydrouracils. Synthesis. 2010 Feb;(4):651-660. https://doi.org/10.1055/s-0029-1218587
Olimpieri, Francesca ; Fustero, Santos ; Volonterio, Alessandro ; Zanda, Matteo. / A Mild, Efficient Synthesis of gem-Difluorodihydrouracils. In: Synthesis. 2010 ; No. 4. pp. 651-660.
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AB - Carbodiimides react effectively with beta-aryl/alkyl-beta-hydroxy-alpha,alpha-difluorocarboxylic acids to afford a vast array of fully substituted gem-difluorodihydrouracils through a two step reaction sequence. In the first step, condensation between the two reactants leads in most cases to the formation of a mixture of the desired dihydrouracils and N-acylurea co-products. However, the latter could be easily recovered and efficiently converted into the target compounds. The sequence works well in very mild conditions (CH2Cl2, 20 degrees C) and the reaction resulted to be completely regioselective when asymmetric carbodiimides were used. When the N-acylurea derivatives are not sufficiently stable for isolation, the process could be done in a one-pot fashion leading to the direct formation of the desired dihydrouracils, although in lower yields.

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