Unlocking Catalyst Activation as a Critical Bottleneck in Cross‐Coupling Reactions: Room‐Temperature Couplings of Weak Nucleophiles Enabled by [Pd(1‐MeNAP)TFA] <sub>2</sub> Precatalysts
enable substantial reductions in reaction temperature, often by 80°C, while preserving established ligands and reaction conditions, thereby providing a drop-in solution to existing reactivity limitations. As a result, arylations of amides, carbamates, sulfonamides, amidines, ureas, cyclopropylamines, and trifluoroethylamines can be performed at room-temperature with markedly improved functional-group tolerance and compatibility with sensitive, coordinating heterocycles. Mechanistic studies reveal that catalyst activation, rather than catalytic turnover, has been the principal bottleneck in many cross-coupling reactions.
Authors
- Angelino Doppiu (ORCID: https://orcid.org/0009-0002-0965-5444)
- Nikolaos V. Tzouras (ORCID: https://orcid.org/0000-0003-1718-0207)
- Sourav Manna (ORCID: https://orcid.org/0000-0003-3018-0949)
- Lukas J. Gooßen (ORCID: https://orcid.org/0000-0002-2547-3037)
- Henric F. Janning
- Fadil Faizal Mannighayil
- Jane Anto Simplica Sagayaraj
Institutions
- Umicore (Belgium) (BE)
- Umicore (Germany) (DE)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2026-05-13
- DOI
- https://doi.org/10.1002/anie.3359287
- Primary Topic
- Catalytic Cross-Coupling Reactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Alexander von Humboldt-Stiftung
- Deutsche Forschungsgemeinschaft