Nonheme Manganese-CatalyzedOxidative <i>N</i>‑Dealkylation of Tertiary Amides:Manganese(IV)-Oxo AminopyridineCation Radical Species and Hydride Transfer Mechanism

The development of efficient and practical <i>N</i>-dealkylation reactions stands as a longstanding objective in synthetic chemistry. Inspired by the oxidative <i>N</i>-dealkylation reactions mediated by heme and nonheme metalloenzymes, we disclose a biomimetic oxidative <i>N</i>-dealkylation catalysis that utilizes a nonheme manganese complex bearing anthryl-appended aminopyridine ligand and hydrogen peroxide (H₂O₂) as the terminal oxidant. A variety of Weinreb amides and cyclic aliphatic amines are efficiently transformed into valuable methyl hydroxamates and ω-amino acids through oxidative C–N bond cleavage. Mechanistic studies, including density functional theory (DFT) calculations, reveal that a manganese(IV)-oxo aminopyridine cation radical species, which is formed via the bromoacetic acid-assisted heterolytic O–O bond cleavage of a presumed manganese(III)-hydroperoxo aminopyridine species and the subsequent intramolecular electron transfer (ET) from the anthryl group of the aminopyridine ligand to the manganese center, is the active intermediate that initiates the oxidative <i>N</i>-dealkylation reactions; this process is reminiscent to the heterolytic O–O bond cleavage of iron(III)-hydroperoxo porphyrin intermediates (Cpd 0) to form iron(IV)-oxo porphyrin π-cation radicals (Cpd I) that are responsible for diverse selective oxidation reactions. Moreover, it is revealed that the oxidative activation of the C–H bond adjacent to the nitrogen atom proceeds via a hydride transfer (HT) mechanism, which involves a concerted asynchronous proton-coupled electron transfer (PCET), followed by an ET process. Thus, this study reports the first instance of catalytic oxidative <i>N</i>-dealkylation of a variety of tertiary amides, such as Weinreb amides and cyclic aliphatic amines, mediated by a Cpd I-like nonheme manganese(IV)-oxo aminopyridine cation radical species via an initial HT pathway.