Investigation of macrocyclisation routes to 1,4,7-triazacyclononanes: efficient syntheses from 1,2-ditosylamides

G. Stones, Régis Tripoli, Colin L. McDavid, Kewin Roux-Duplatre, A.R. Kennedy, D.C. Sherrington, C.L. Gibson

Research output: Contribution to journalArticle

10 Citations (Scopus)
397 Downloads (Pure)

Abstract

Two routes to the synthesis of a cyclohexyl-fused 1,4,7-triazacyclononane involving macrocyclisations of tosamides have been investigated. In the first approach, using a classic Richman-Atkins-type cyclisation of a cyclohexyl-substituted 1,4,7-tritosamide with ethylene glycol ditosylate, afforded the cyclohexyl-fused 1,4,7-triazacyclononane in 5.86% overall yield in four steps. The second, more concise, approach involving the macrocyclisation of trans-cyclohexane-1,2-ditosamide with the tritosyl derivative of diethanolamine initially gave poor yields (< 25%). The well-documented problems with efficiencies in macrocyclisations using 1,2-ditosamides led to the use of a wider range of 1,2-ditosamides including ethane-1,2-ditosamide and propane-1,2-ditosamide. These extended studies led to the development of an efficient macrocyclisation protocol using lithium hydride. This new method afforded 1,4,7-tritosyl-1,4,7-triazacyclononanes in good yield (57-90%) from 1,2-ditosamides in a single step. These efficient methods were then applied to the preparation of a chiral cyclohexyl-fused 1,4,7-tritosyl-1,4,7-triazacyclononane (65-70%). This key chiral intermediate was then converted into a copper(II) complex following detosylation and N-methylation. The resulting chiral copper(II) complex catalysed the aziridination of styrene but it did so in a racemic fashion.
Original languageEnglish
Pages (from-to)374-384
Number of pages11
JournalOrganic and Biomolecular Chemistry
Volume6
Issue number2
Early online date11 Dec 2007
DOIs
Publication statusPublished - 2008

    Fingerprint

Keywords

  • chiral aziridines
  • crystal structure
  • dynamic behavior
  • model complexes
  • ring closure
  • ligands

Cite this