Anion-Controlled Synthesis of Novel Guanidine-Substituted Oxanorbornanes

Int J Mol Sci. 2022 Dec 16;23(24):16036. doi: 10.3390/ijms232416036.


The cycloaddition of simple alkyl-substituted guanidine derivatives is an interesting approach toward polycyclic superbases and guanidine-based organocatalysts. Due to the high nucleophilicity of guanidines, an aza-Michael reaction with dienophiles is more common and presents a huge obstacle in achieving the desired synthetic goal. Our preliminary investigations indicated that the proton could act as a suitable protecting group to regulate the directionality of the reaction. To investigate the role of the protonation state and type of anion, the reactivity of furfuryl guanidines with dimethyl acetylenedicarboxylate was explored. Furfuryl guanidines showed a strong reaction dependence on the nucleophilicity of the counterion and the structure of guanidine. While the reaction of DMAD with the guanidinium halides provided products of an aza-Michael addition, Diels-Alder cycloaddition occurred if non-nucleophilic hexafluorophosphate salts were used. Depending on the structure and the reaction conditions, oxanorbornadiene products underwent subsequent intramolecular cyclization. A tendency toward intramolecular cyclization was interpreted in terms of the pKa of different positions of the guanidine functionality in oxanorbornadienes. New polycyclic guanidines had a slightly decreased pKa in acetonitrile and well-defined geometry suitable for the buildup of selective sensors.

Keywords: acidity; aza-Michael reaction; cycloaddition; guanidines; halide anion; hexafluorophosphate; oxanorbornane.

MeSH terms

  • Anions
  • Cyclization
  • Guanidine / chemistry
  • Guanidines* / chemistry


  • Guanidine
  • Guanidines
  • Anions