Electrochemical Carboxylation of Aldehydes with CO₂: Mechanistic Insights and Enantioselective Synthesis

Author: Ton, Thu Nu Minh

Year: 2026

Degree: Dissertation (Ph.D.)

Advisor: Manthiram, Karthish

Committee Members: See, Kimberly; Stoltz, Brian M.; Cushing, Scott K.; Manthiram, Karthish

Option: Chemistry

Abstract

The electrochemical carboxylation of organic substrates with CO₂ is a promising strategy for the sustainable synthesis of value-added carboxylic acids, offering mild operating conditions and avoiding the need for highly reactive organometallic reagents. As the electrical grid transitions toward renewable energy sources, electrochemical activation of CO₂ is poised to become an increasingly carbon-negative process, further improving the sustainability of chemical manufacturing. Despite these advantages, the scope of electrochemical carboxylation remains limited, and a deeper mechanistic understanding is needed to guide rational improvements in selectivity and efficiency. This thesis addresses these gaps by investigating the electrochemical carboxylation of aldehydes, an underexplored but industrially relevant substrate class, and demonstrating for the first time that this transformation can be performed enantioselectively.

For aromatic aldehydes, electroanalytical and spectroscopic studies support a mechanism in which a substrate-derived ketyl radical couples with CO₂ to form the α-hydroxy carboxylic acid product. EPR spectroscopy provided direct evidence for formation of the ketyl radical intermediate under electrolytic conditions, and kinetic studies identified the coupling step as the rate-determining step. Lewis acidic additives such as MgCl2 were found to play a key role in promoting ketyl radical formation. Extending this chemistry to aliphatic aldehydes revealed that their more negative reduction potentials open an alternative CO₂ reduction pathway towards electrochemical carboxylation. However, it was also found that polymerization of the substrate under reductive conditions limits carboxylation selectivity, prompting future works to understand and develop strategies towards mitigating the polymerization pathway.

Building on this mechanistic foundation, the first enantioselective electrochemical carboxylation of an aldehyde was demonstrated using chiral metal salen complexes as homogeneous catalysts, affording optically active mandelic acid with up to 43% enantiomeric excess. Both the applied potential and metal center identity were found to strongly influence enantioselectivity, pointing to an electronic basis for stereocontrol. Cyclic voltammetry studies further suggest that the most effective catalysts readily undergo reductive activation under the applied conditions, enabling coordination with CO₂ to initiate the enantioselective pathway. Taken together, the insights developed in this thesis provide a foundation for the rational design of more selective, efficient, and enantiocontrolled electrochemical CO₂ incorporation strategies.