Synthesis of Amidines Via P(III)/P(V)=O Redox Catalyzed In Situ Formation of Imidoyl Chlorides From Amides

article Synthesis of Amidines Via P(III)/P(V)=O Redox Catalyzed In Situ Formation of Imidoyl Chlorides From Amides published Viktorija Medvaric author 92677 Jan Paradies author 533390000-0002-3698-668X Thomas Werner author 892710000-0001-9025-3244 2 department 389 department Amidines are a ubiquitous class of bioactive compounds found in a wide variety of natural products; thus, efficient strategies for their preparation are in great demand. Herein, a novel protocol is reported for the synthesis of amidines based on PIII/PVO redox catalysis. This two‐step, one‐pot approach involves the activation of amides via PIII/PVO catalyzed in situ formation of imidoyl chloride intermediates which are directly converted upon reaction with amines into the corresponding amidines. Instead of traditionally used toxic and corrosive chloride sources, hexachloroacetone (HCA) is successfully employed as a halide source. The reaction proceeds with low catalyst loading (2 mol%) in BuOAc as the solvent. Under the optimized conditions, 20 amidines are prepared in yields up to 99%. A feasible mechanism is proposed based on experimental results. The synthetic potential of this method is evaluated in the preparation of the tyrosine kinase inhibitor (TKI) Erlotinib. Wiley2025 eng T2TCSSD Advanced Synthesis and Catalysis 1615-4150 1615-416910.1002/adsc.70059 V. Medvaric, J. Paradies, T. Werner, Advanced Synthesis and Catalysis (2025). Medvaric, Viktorija, Jan Paradies, and Thomas Werner. “Synthesis of Amidines Via P(III)/P(V)=O Redox Catalyzed In Situ Formation of Imidoyl Chlorides From Amides.” Advanced Synthesis and Catalysis, 2025. <a href="https://doi.org/10.1002/adsc.70059">https://doi.org/10.1002/adsc.70059</a>. Medvaric, V., Paradies, J., & Werner, T. (2025). Synthesis of Amidines Via P(III)/P(V)=O Redox Catalyzed In Situ Formation of Imidoyl Chlorides From Amides. Advanced Synthesis and Catalysis, Article 202500394. <a href="https://doi.org/10.1002/adsc.70059">https://doi.org/10.1002/adsc.70059</a> V. Medvaric, J. Paradies, and T. Werner, “Synthesis of Amidines Via P(III)/P(V)=O Redox Catalyzed In Situ Formation of Imidoyl Chlorides From Amides,” Advanced Synthesis and Catalysis, Art. no. 202500394, 2025, doi: <a href="https://doi.org/10.1002/adsc.70059">10.1002/adsc.70059</a>. Medvaric V, Paradies J, Werner T. Synthesis of Amidines Via P(III)/P(V)=O Redox Catalyzed In Situ Formation of Imidoyl Chlorides From Amides. Advanced Synthesis and Catalysis. Published online 2025. doi:<a href="https://doi.org/10.1002/adsc.70059">10.1002/adsc.70059</a> @article{Medvaric_Paradies_Werner_2025, title={Synthesis of Amidines Via P(III)/P(V)=O Redox Catalyzed In Situ Formation of Imidoyl Chlorides From Amides}, DOI={<a href="https://doi.org/10.1002/adsc.70059">10.1002/adsc.70059</a>}, number={202500394}, journal={Advanced Synthesis and Catalysis}, publisher={Wiley}, author={Medvaric, Viktorija and Paradies, Jan and Werner, Thomas}, year={2025} } Medvaric, Viktorija, et al. “Synthesis of Amidines Via P(III)/P(V)=O Redox Catalyzed In Situ Formation of Imidoyl Chlorides From Amides.” Advanced Synthesis and Catalysis, 202500394, Wiley, 2025, doi:<a href="https://doi.org/10.1002/adsc.70059">10.1002/adsc.70059</a>. 613352025-09-17T15:16:49Z2025-11-10T08:44:04Z