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

<jats:p>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 P<jats:sup>III</jats:sup>/P<jats:sup>V</jats:sup>O redox catalysis. This two‐step, one‐pot approach involves the activation of amides via P<jats:sup>III</jats:sup>/P<jats:sup>V</jats:sup>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.</jats:p>