Electrochemical Platform for Automated Design-of-Experiment Optimization of Ni-Catalyzed Cross-Electrophile Coupling Reactions.
- 1Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
- 2Drug Substance Technologies - Synthetics, Process Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, United States.
Abstract
Electrosynthetic organic reactions have advanced significantly in recent years, but their adoption for large-scale applications remains limited. Here, we report an automated experimental platform designed to facilitate translation of small-scale chemical and electrochemical redox reactions into robust larger-scale electrochemical processes. This platform, which integrates a commercial chemical synthesis workstation, peristaltic pumps, and a potentiostat, is equipped to conduct an automated sequence of batch experiments to optimize standard variables, such as stir rate and temperature, in addition to variables unique to electrosynthesis, such as applied current and total charge passed. Analysis of these variables using a design-of-experiment (DoE) approach accelerates identification of optimal reaction conditions and translation of mg-to-multigram operations. To evaluate the DoE optimization protocol and experimental platform, four Ni-catalyzed C-(sp2)-C-(sp3) cross-electrophile coupling reactions were selected from the literature that were originally conducted on a 0.2-0.4 mmol scale with chemical or electrochemical reduction methods. Each reaction was successfully scaled by a factor of 30-250, delivering up to 20 g (100 mmol) of isolated product. These results show how small-scale redox reactions may be rapidly translated to scalable electrosynthetic processes.
Related
- Noninnocent Deep Eutectic Solvents Enable Selective, Sustainable Nickel‐Catalyzed Cross‐Electrophile Couplings to Diarylmethanes
- RxnScout: Deploying a Vision-Language Agent for Nickel-Catalyzed C-Glycosylation Condition Optimization
- Optimization of Sodium-Catalyzed Si–N Bond Formation Through a Comparative Study of Group 1 Alkoxides
- Optimization of the intramolecular cyclization to form the clozapine lactam intermediate under continuous-flow conditions and elucidation of the H2SO4-catalyzed mechanism by DFT
- Optimization of Base-Catalyzed Transesterification toward Maximum Biodiesel Yield from Camelus dromedarius Fat Waste
BibTeX
@article{chen2026electrochemical,
title = {{Electrochemical Platform for Automated Design-of-Experiment Optimization of Ni-Catalyzed Cross-Electrophile Coupling Reactions.}},
author = {Jieping Chen and Mathew R Johnson and Zhifeng Tan and Tessa H T Myren and Kyle W Quasdorf and Carolyn S Wei and Shannon S Stahl},
journal = {JACS Au},
year = {2026},
month = sep,
doi = {10.1021/jacsau.6c01220},
url = {https://europepmc.org/article/MED/42953179},
note = {CC BY},
}
RIS
TY - JOUR
TI - Electrochemical Platform for Automated Design-of-Experiment Optimization of Ni-Catalyzed Cross-Electrophile Coupling Reactions.
AU - Jieping Chen
AU - Mathew R Johnson
AU - Zhifeng Tan
AU - Tessa H T Myren
AU - Kyle W Quasdorf
AU - Carolyn S Wei
AU - Shannon S Stahl
PY - 2026
DA - 2026/09/22
JO - JACS Au
DO - 10.1021/jacsau.6c01220
UR - https://europepmc.org/article/MED/42953179
AB - Electrosynthetic organic reactions have advanced significantly in recent years, but their adoption for large-scale applications remains limited. Here, we report an automated experimental platform designed to facilitate translation of small-scale chemical and electrochemical redox reactions into robust larger-scale electrochemical processes. This platform, which integrates a commercial chemical synthesis workstation, peristaltic pumps, and a potentiostat, is equipped to conduct an automated sequence of batch experiments to optimize standard variables, such as stir rate and temperature, in addition to variables unique to electrosynthesis, such as applied current and total charge passed. Analysis of these variables using a design-of-experiment (DoE) approach accelerates identification of optimal reaction conditions and translation of mg-to-multigram operations. To evaluate the DoE optimization protocol and experimental platform, four Ni-catalyzed C-(sp2)-C-(sp3) cross-electrophile coupling reactions were selected from the literature that were originally conducted on a 0.2-0.4 mmol scale with chemical or electrochemical reduction methods. Each reaction was successfully scaled by a factor of 30-250, delivering up to 20 g (100 mmol) of isolated product. These results show how small-scale redox reactions may be rapidly translated to scalable electrosynthetic processes.
SN - 2691-3704
ER -