Issue 2, 2008

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

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
01 Nov 2007
Accepted
20 Nov 2007
First published
11 Dec 2007

Org. Biomol. Chem., 2008,6, 374-384

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

G. Stones, R. Tripoli, C. L. McDavid, K. Roux-Duplâtre, A. R. Kennedy, D. C. Sherrington and C. L. Gibson, Org. Biomol. Chem., 2008, 6, 374 DOI: 10.1039/B716938H

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