Iron-Catalyzed Alkylation-Reduction of N-Methyl Nitrones via LMCT Activation

铁催化N-甲基硝酮的LMCT活化烷基化还原反应

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Abstract

N-Monomethyl secondary amines are privileged structural motifs that frequently occur in pharmaceuticals and bioactive molecules. However, their synthesis often requires harsh conditions or suffers from poor selectivity. Here, we report a redox-neutral, iron-catalyzed strategy that enables the efficient formation of these motifs via a tandem alkylation-reduction of (Z)-N-methyl nitrones. The transformation proceeds through an Fe(III)-mediated ligand-to-metal charge transfer (LMCT) process that generates alkyl radicals from readily available carboxylic acids under visible light irradiation, followed by Fe(II)-promoted N-O bond cleavage of the resulting hydroxylamines. This dual catalytic reactivity provides a straightforward and sustainable route to N-monomethyl amines under mild conditions, without the need for exogenous reductants, ligands, or precious metals. The method exhibits a broad substrate scope, excellent functional group tolerance, and high selectivity, highlighting its potential as a practical platform for late-stage amine diversification.

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