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PreprintCC BYChemRxiv

In Situ Co-Activation–Nucleophilic Aromatic Substitution (ISCA–SNAR): Synthesis of a-Aryl-a-Heteroarylmalononitriles.

  • Avneesh Kumar1,2
  • Akash Gogate1,2
  • Alexander Grenning1,2
  1. 1Department of Chemistry
  2. 2University of Minnesota
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Abstract

We report the discovery of a fundamentally unique nucleophilic aromatic substitution (S N Ar) reaction. It was found that a-arylmalononitriles and haloheterocycles undergo a mild, additive- and base-free C–C bond forming reaction via in situ co-activation (ISCA) to a carbanion and a pyridinium, which rapidly react through a neutral and low-barrier Meisenheimer complex to ultimately yield the S N Ar product. This study includes a background analysis of ISCA-S N Ar and a-aryl-a-heteroarylmalononitriles, discovery and optimization of efficient coupling conditions, a study of various physical organic parameters governing the transformation, scope of the reaction, and select malononitrile functional group interconversions. These detailed studies lay the groundwork for developing this, and related reactions, for use in high-value organic synthesis.

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Cite

BibTeXRIS
BibTeX
@misc{kumar2026situ,
  title = {{In Situ Co-Activation–Nucleophilic Aromatic Substitution (ISCA–SNAR): Synthesis of a-Aryl-a-Heteroarylmalononitriles.}},
  author = {Avneesh Kumar and Akash Gogate and Alexander Grenning},
  howpublished = {ChemRxiv},
  year = {2026},
  month = sep,
  doi = {10.26434/chemrxiv.15000950/v2},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15000950/v2},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - In Situ Co-Activation–Nucleophilic Aromatic Substitution (ISCA–SNAR): Synthesis of a-Aryl-a-Heteroarylmalononitriles.
AU  - Avneesh Kumar
AU  - Akash Gogate
AU  - Alexander Grenning
PY  - 2026
DA  - 2026/09/15
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15000950/v2
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15000950/v2
AB  - We report the discovery of a fundamentally unique nucleophilic aromatic substitution (S N Ar) reaction. It was found that a-arylmalononitriles and haloheterocycles undergo a mild, additive- and base-free C–C bond forming reaction via in situ co-activation (ISCA) to a carbanion and a pyridinium, which rapidly react through a neutral and low-barrier Meisenheimer complex to ultimately yield the S N Ar product. This study includes a background analysis of ISCA-S N Ar and a-aryl-a-heteroarylmalononitriles, discovery and optimization of efficient coupling conditions, a study of various physical organic parameters governing the transformation, scope of the reaction, and select malononitrile functional group interconversions. These detailed studies lay the groundwork for developing this, and related reactions, for use in high-value organic synthesis.
ER  -