Planar-Chiral Macrobicycles Comprising Cyclam Moiety

Abstract

Macrobicycles derived from 1,8-disubstituted cyclam in principle may be planar-chiral provided that the second chain cannot rotate around the cyclam fragment. Hindered rotation is enabled by the introduction of two additional substituents at nitrogen atoms and by enough short chain which forms the second cycle. N,N’,N”,N’”-tetrasubstituted cyclams bearing two 3-bromobenzyl and two arylmethyl substituents were synthesized starting from protected bis-formaldehydecyclam. These compounds were introduced in the Pd-catalyzed amination reactions with 1,3-diaminopropane, 1,2diaminoethane and 1,2-diphenyl-1,2-diaminoethane to form corresponding macrobicycles. Various chiral diphosphine ligands were tested in these reactions and asymmetric induction was noted in some cases. The pronounced dependence of the chemical yields and enantiomeric excess on the nature of the starting compounds and chiral phosphine ligand was observed. The highest chemical yields of macrobicycles reached 50 %, the best enantiomeric excess was 13 % when using Josiphos-type ferrocene-based ligand.