Synthesis of C2-symmetric aza- and azaoxa-macrocyclic ligands derived from (1R,2R)-1,2-diaminocyclohexane and their applications in catalysis

Abstract

Investigations have been undertaken into the synthesis of chiral derivatives of 1,4,7-triazacyclononane and 1,7-diaza-4-oxacyclononane that incorporate the C₂-symmetric (R,R)-1,2-diaminocyclohexane backbone. The target ligands 17a and 17b have been prepared as their hydrochloride salts, the latter of which has been characterized by single crystal X-ray diffraction revealing an extensively hydrogen bonded polymeric network in the solid state. These investigations have shown that the formation of the fused bicyclic system in these ligands via standard Richman–Atkins macrocyclisation conditions is extremely difficult, particularly for the intermediate 16a, when three tosyl amide nitrogen atoms must be accommodated in the macrocyclic ring. In addition to these target ligands the unexpected piperazine 15 as well as the novel binucleating ligand 19 have also been prepared. Preliminary investigation into the coordination chemistry of 17b resulted in the formation of the copper(II) complex [Cu(17b)Cl₂] in which the copper centre exists in the expected square-pyramidal geometry with the two chloride ions and the nitrogen donors occupying the equatorial positions and with the oxygen donor apically situated. The complex has been screened for activity and found to be a potent catalyst for two hetero-Diels–Alder reactions. The first aza-Diels–Alder reaction of imine 20 with Danishefsky's diene 21 proceeds to yield the cycloadduct 22 in 94% yield. The second nitroso-Diels–Alder reaction relies on the in situ oxidation of hydroxylamine 23 to dienophile 24, catalysed by the complex in the presence of tert-butyl hydroperoxide, which is then trapped as cycloadduct 25 by cyclohexadiene in 69% yield.