Protonated Chiral 1,2-Diamine Organocatalysts for N-Selective Nitroso Aldol Reaction

Jae Ho Shim, Ji Yeon Lee, Hyeon Soo Kim, Deok Chan Ha

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


The introduction of nitrogen to carbonyl groups is considered both challenging and highly desirable by those who work in the field of organic synthesis. In this study, a diphenylethylenediamine-derived catalyst demonstrating N-selectivity was designed using a quantum calculation for the nitroso aldol reaction. The reductive monoalkylation of (R,R)-(+)-1,2-diphenylethylenediamine afforded an organic chiral diamine catalyst in high yield. The expected reaction mechanism for the nitroso aldol reaction was determined, and the product and solvent conditions were optimized through quantum calculations. The calculation results revealed that the enantioselectivity is determined by the hydrogen bond between the alkyl substituent of the chiral diamine and the oxygen of the aromatic aldehyde on the ammonium moiety. The reaction was found to proceed optimally in the presence of 5 mol % catalyst at −10 C in brine. Using these conditions, an eco-friendly nitroso aldol reaction was performed in which the organic catalyst and cyclohexanone formed enamine. Nitrosobenzene, activated by hydrogen bonding with an ammonium catalyst, was used to minimize the steric hindrance between the catalyst and the reactant, resulting in high enantioselectivity. A nitroso aldol product with high N-selectivity and enantioselectivity (98% ee) was obtained in 95% yield. The catalyst developed in this study provides a less expensive and more environmentally friendly alternative for the nitroso aldol reaction.

Original languageEnglish
Article number435
Issue number4
Publication statusPublished - 2022 Apr

Bibliographical note

Funding Information:
Funding: This study was supported by the National Research Foundation (NRF) and funded by the Korean government (MSIT) (2021R1A6A3A01087948). This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Korean government (MSIT) (2021M3A9G1097744). In addition, this study was supported by a Korea University grant.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • enantioselectivity
  • nitroso aldol reaction
  • organocatalyst
  • regioselectivity

ASJC Scopus subject areas

  • Catalysis
  • Environmental Science(all)
  • Physical and Theoretical Chemistry


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