Work

In Situ Co-Activation-Nucleophilic Aromatic Substitution (ISCA-S N Ar): Synthesis of α-Aryl-α-Heteroarylmalononitriles

Year: 2026

Type: article

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.

Source: Chemical Science

DOI: 10.1039/d6sc07107d

Authors: Avneesh Kumar, Akash R Gogate, Daniel Gibney, Jan-Niklas Boyn, Alexander Grenning

Institution: University of Minnesota

Language: English

Topic: Catalytic Cross-Coupling Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: diamond

Funders: University of Minnesota, College of Science and Engineering, University of Minnesota

OpenAlex ID: W7213313140