Volume 247, 2023

Electrochemical hydrogen isotope exchange of amines controlled by alternating current frequency

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.

Graphical abstract: Electrochemical hydrogen isotope exchange of amines controlled by alternating current frequency

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
18 feb 2023
Accepted
13 mar 2023
First published
13 mar 2023

Faraday Discuss., 2023,247, 45-58

Author version available

Electrochemical hydrogen isotope exchange of amines controlled by alternating current frequency

N. Behera, D. Gunasekera, J. P. Mahajan, J. Frimpong, Z. Liu and L. Luo, Faraday Discuss., 2023, 247, 45 DOI: 10.1039/D3FD00044C

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