Discovery of biomimetic iron-catalyzed mechanism for C H amination of alkylamine compounds and mechanism-guided design

The regio- and stereo-selectivity activation of CH bond catalyzed by CYP450 has attracted much attention due to its high efficiency. In these reactions, a pair of high-valent iron-oxo and iron-hydroxo species called compound I (Cpd I) and II (Cpd II) are the main intermediates. Studies on the conversion of lidocaine analogs into imidazolinones reveal that the cyclization process, whether it involves a one-step hydrogen abstraction mediated by Cpd I or a secondary selective hydrogen abstraction facilitated by Cpd II, is contingent upon the spin state of the P450 active center and the specific structure of the organic compound. Based on the research findings, it is suggested that inserting a carbon atom at a specific position to elongate the carbon chain length represents an effective approach for producing piperazinone. The mechanistic investigation can offer valuable insights for the rational design of organic compounds and facilitate a deeper comprehension of P450.