Triple Atom Transfer-Enabled α-C(sp3)-H Aminomethylation of Aliphatic Amines: General and Modular Access to Vicinal Diamines
- 1School of Chemistry and Chemical Engineering
- 2Nanchang University Nanchang
Abstract
Vicinal diamines are prevalent structural elements in organic molecules. In particular, those featuring a tertiary alkylamine motif are commonly found in biologically active molecules and therapeutic agents. However, methods for the efficient construction of these architectures from inexpensive and readily available feedstocks remain scarce. Here, we report a mild photocatalytic protocol for the modular synthesis of vicinal alkyl diamines via triple atom transfer-enabled α-C(sp3)–H aminomethylation. This transformation integrates halogen-atom transfer (XAT) and intramolecular 1,5-hydrogen-atom transfer (HAT) processes to furnish key α-amido alkyl radicals, which subsequently add to in situ-generated iminium ions. Critical to the success of the reaction is the cooperative action of a nickel complex and a zinc salt, which jointly promote the aminomethylation process. Utility of this method is demonstrated through late-stage modification of complex amine molecules, scale-up experiments, and ready access to scaffold-diverse free vicinal diamines. In addition, compatibility with aromatic aldehydes and the ability to functionalize alternative C–H sites further expand the chemical space of diamine architectures, highlighting the robustness and synthetic versatility of this protocol.
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BibTeX
@misc{chen2026triple,
title = {{Triple Atom Transfer-Enabled α-C(sp3)-H Aminomethylation of Aliphatic Amines: General and Modular Access to Vicinal Diamines}},
author = {Yu Chen and Caiyun He and Huanyu Xiao and Zhaoyang Xu and Weiran Yang and Tao Yang},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010434/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010434/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Triple Atom Transfer-Enabled α-C(sp3)-H Aminomethylation of Aliphatic Amines: General and Modular Access to Vicinal Diamines
AU - Yu Chen
AU - Caiyun He
AU - Huanyu Xiao
AU - Zhaoyang Xu
AU - Weiran Yang
AU - Tao Yang
PY - 2026
DA - 2026/10/13
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010434/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010434/v1
AB - Vicinal diamines are prevalent structural elements in organic molecules. In particular, those featuring a tertiary alkylamine motif are commonly found in biologically active molecules and therapeutic agents. However, methods for the efficient construction of these architectures from inexpensive and readily available feedstocks remain scarce. Here, we report a mild photocatalytic protocol for the modular synthesis of vicinal alkyl diamines via triple atom transfer-enabled α-C(sp3)–H aminomethylation. This transformation integrates halogen-atom transfer (XAT) and intramolecular 1,5-hydrogen-atom transfer (HAT) processes to furnish key α-amido alkyl radicals, which subsequently add to in situ-generated iminium ions. Critical to the success of the reaction is the cooperative action of a nickel complex and a zinc salt, which jointly promote the aminomethylation process. Utility of this method is demonstrated through late-stage modification of complex amine molecules, scale-up experiments, and ready access to scaffold-diverse free vicinal diamines. In addition, compatibility with aromatic aldehydes and the ability to functionalize alternative C–H sites further expand the chemical space of diamine architectures, highlighting the robustness and synthetic versatility of this protocol.
ER -