Investigation of macrocyclisation routes to 1,4,7-triazacyclononanes: efficient syntheses from 1,2-ditosylamides.
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.
Stones
Graham
G
Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, UKG1 1XL.
Tripoli
Régis
R
McDavid
Colin L
CL
Roux-Duplâtre
Kewin
K
Kennedy
Alan R
AR
Sherrington
David C
DC
Gibson
Colin L
CL
D000577:Amides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D014105:Tosyl Compounds / Q000737:chemistry*
D000577:Amides; D006571:Heterocyclic Compounds; D014105:Tosyl Compounds; C075712:1,4,7-triazacyclononane