Photochemical Aminomethylation of C(sp ³ )–H Bonds via Hydrogen Atom Transfer
- 1Flow Chemistry Group, Van ’t Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Science Park 904, Amsterdam, Netherlands, 1098 XH
Abstract
Direct installation of an aminomethyl group onto aliphatic C–H bonds provides an attractive route to valuable amine-containing building blocks but remains challenging with conventional polar approaches. Here, we report a photochemical aminomethylation of C(sp3)–H bonds enabled by hydrogen atom transfer (HAT). Photoexcited benzophenone directly abstracts hydrogen from αamino, α-oxy, and α-thio C–H bonds, generating carbon-centered radicals that are intercepted by an in situ-formed N-protected formimine. This strategy provides direct access to protected vicinal diamines, amino alcohol derivatives, and related aminomethylated products without requiring prefunctionalization of the C–H donor. Notably, the C–H substrate can be employed as the limiting reagent, while selective radical generation suppresses overfunctionalization. Translation to continuous flow reduces reaction times from 20 h to 3 h, while improving yields for the investigated substrates, and enables scalable synthesis. Subsequent deprotection and functionalization further demonstrate the synthetic utility of the resulting aminomethylated products.
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BibTeX
@misc{akdeniz2026photochemical,
title = {{Photochemical Aminomethylation of C(sp ³ )–H Bonds via Hydrogen Atom Transfer}},
author = {Merve Akdeniz and Lorenzo Di Terlizzi and Jonas Djossou and Timothy Noel},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010233/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010233/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Photochemical Aminomethylation of C(sp ³ )–H Bonds via Hydrogen Atom Transfer
AU - Merve Akdeniz
AU - Lorenzo Di Terlizzi
AU - Jonas Djossou
AU - Timothy Noel
PY - 2026
DA - 2026/10/11
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010233/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010233/v1
AB - Direct installation of an aminomethyl group onto aliphatic C–H bonds provides an attractive route to valuable amine-containing building blocks but remains challenging with conventional polar approaches. Here, we report a photochemical aminomethylation of C(sp3)–H bonds enabled by hydrogen atom transfer (HAT). Photoexcited benzophenone directly abstracts hydrogen from αamino, α-oxy, and α-thio C–H bonds, generating carbon-centered radicals that are intercepted by an in situ-formed N-protected formimine. This strategy provides direct access to protected vicinal diamines, amino alcohol derivatives, and related aminomethylated products without requiring prefunctionalization of the C–H donor. Notably, the C–H substrate can be employed as the limiting reagent, while selective radical generation suppresses overfunctionalization. Translation to continuous flow reduces reaction times from 20 h to 3 h, while improving yields for the investigated substrates, and enables scalable synthesis. Subsequent deprotection and functionalization further demonstrate the synthetic utility of the resulting aminomethylated products.
ER -