On the macrocyclization selectivity of meta-substituted diamines and dialdehydes: towards macrocycles with tunable functional peripheries

Abstract

The efficient preparation of functional rigid and soluble macrocycles remains a challenge for synthetic chemists. Here, we exploit the thermodynamic control of dynamic covalent chemistry to investigate the influence of the monomer structure on the macrocyclization selectivity. A series of rigid cyclic hexamer has been synthesized by imine condensation of benzene building blocks, i.e. meta-substituted diamines and dialdehydes, templated by calcium(II) chloride. The monomers were designed to feature various additional functional groups either available for further post-cyclization modifications or acting as solubilizing groups. The cyclization selectivity was systematically investigated and optimized depending on the length of the applied solubilizing group and on the nature of the additional functional group. A selectivity up to 92% was reached for the macrocyclization exhibiting trifluoromethyl and bromine groups at the outer periphery and hydroxyl groups in the cavity.

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Acknowlegdements

Christopher Barner-Kowollik is acknowledges a Laureate Fellowship from the Australian Research Council (ARC) and continued key support from the Queensland University of Technology (QUT). The authors would like to thank T. Sattelberger, C. Albrecht and T. Anh for experimental support.

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Correspondence to Audrey Llevot or Michael A. R. Meier.

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Klein, G., Llevot, A., Löser, P. et al. On the macrocyclization selectivity of meta-substituted diamines and dialdehydes: towards macrocycles with tunable functional peripheries. J Incl Phenom Macrocycl Chem 95, 119–134 (2019). https://doi.org/10.1007/s10847-019-00931-9

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Keywords

  • Macrocycle
  • Template
  • Schiff base
  • Selectivity