Electrochemical Hydrogen Isotope Exchange of Amines Controlled by Alternating Current Frequency
Journal: Faraday Discuss. (2023) · 247 · pp. 45–58 · Publication #91
Abstract
Here, we report an electrochemical protocol for hydrogen isotope exchange (HIE) at α-C(sp3)–H amine sites. Tetrahydroisoquinoline and pyrrolidine are selected as two model substrates because of their different proton transfer (PT) and hydrogen atom transfer (HAT) kinetics at the α-C(sp3)–H amine sites, which are utilized to control the HIE reaction outcome at different applied alternating current (AC) frequencies. We found the highest deuterium incorporation for tetrahydroisoquinolines at 0 Hz (i.e., under direct current (DC) electrolysis conditions) and pyrrolidines at 0.5 Hz. Analysis of the product distribution and D isotope incorporation at different frequencies reveals that the HIE of tetrahydroisoquinolines is limited by its slow HAT, whereas the HIE of pyrrolidines is limited by the overoxidation of its α-amino radical intermediates. The AC-frequency-dependent HIE of amines can be potentially used to achieve selective labeling of α-amine sites in one drug molecule, which will significantly impact the pharmaceutical industry.
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Citation
@article{D3FD00044C,
author ="Behera, Nibedita and Gunasekera, Disni and Mahajan, Jyoti P. and Frimpong, Joseph and Liu, Zhen-Fei and Luo, Long",
title ="Electrochemical hydrogen isotope exchange of amines controlled by alternating current frequency",
journal ="Faraday Discuss.",
year ="2023",
volume ="247",
issue ="0",
pages ="45-58",
publisher ="The Royal Society of Chemistry",
doi ="10.1039/D3FD00044C",
url ="http://dx.doi.org/10.1039/D3FD00044C",
abstract ="Here{,} we report an electrochemical protocol for hydrogen isotope exchange (HIE) at α-C(sp3)–H amine sites. Tetrahydroisoquinoline and pyrrolidine are selected as two model substrates because of their different proton transfer (PT) and hydrogen atom transfer (HAT) kinetics at the α-C(sp3)–H amine sites{,} which are utilized to control the HIE reaction outcome at different applied alternating current (AC) frequencies. We found the highest deuterium incorporation for tetrahydroisoquinolines at 0 Hz (i.e.{,} under direct current (DC) electrolysis conditions) and pyrrolidines at 0.5 Hz. Analysis of the product distribution and D isotope incorporation at different frequencies reveals that the HIE of tetrahydroisoquinolines is limited by its slow HAT{,} whereas the HIE of pyrrolidines is limited by the overoxidation of its α-amino radical intermediates. The AC-frequency-dependent HIE of amines can be potentially used to achieve selective labeling of α-amine sites in one drug molecule{,} which will significantly impact the pharmaceutical industry."
}