Electrochemical Generation of Ketyl Radicals and Their Applications

Abstract

Ketyl radicals display new reactivities beyond the intrinsic electrophilicity of carbonyls. Recent progress in organic electrosynthesis has fueled the generation and utilization of ketyl radicals under ‘greener’ conditions. This graphical review summarizes these electrochemical advancements into three major categories: cross-pinacol couplings, coupling of carbonyls with alkyl radical precursors, and coupling of carbonyls with unsaturated systems (alkenes, alkynes, cyanoarenes, and N-heterocycles).

Key words

ketyl radicals - umpolung - electrosynthesis - electroreduction - carbonyl

Biographical Sketches

Zhoumei Tan obtained her bachelor’s degree from Nanyang Normal University in 2019. She is currently a Ph.D. student at Beijing University of Technology under the guidance of Dr. Kun Xu. Her research interests focus on alcohol transformations under electrophotochemical conditions.

Kun Xu completed his Ph.D. in 2014 via a collaborative program between the University of Science and Technology of China (USTC) and Rutgers University (RU), supervised by Prof. Zhiyong Wang (USTC) and Prof. Xumu Zhang (RU). Currently, he is working at Beijing University of Technology as a professor of organic chemistry. His research focuses on organic electrosynthesis and electrophotocatalysis.

Chengchu Zeng completed his Ph.D. training at the Institute of Chinese Academy of Sciences (ICCAS) with Prof. Zhi-tang Huang in 2001. He subsequently worked with Prof. J. Y. Becker as a post-doctoral researcher at Ben-Gurion University in Israel. He began his independent career at Beijing University of Technology in August 2003 and was promoted to associate professor in 2003 and full professor in 2010. In 2011, he joined Prof. R. D. Little’s group at UC Santa Barbara (UCSB) as a visiting scholar. His research interests focus on the interface of organic chemistry and electrochemistry, and in particular on the electrosynthesis of fine chemicals.

Ketyl radicals have been widely used in modern organic synthesis to construct value-added alcohols from carbonyl compounds. In contrast to the intrinsic electrophilicity of carbonyls, the nucleophilic ketyl radicals display complementary reactivities with respect to the reaction scope.[1] For this reason, the generation of ketyl radicals under mild conditions is of high synthetic value. Traditionally, the generation of ketyl radicals from carbonyl compounds has relied on the use of SmI₂ or active metals such as K, Sn, and Ti, but the requirement for stoichiometric quantities of metals or metal salts diminishes the synthetic utility of this approach. Recently, the rapid development of photoredox chemistry has stimulated a resurgence of interest in the chemistry of ketyl radicals since it represents a milder strategy for obtaining such radicals. However, due to the high reduction potential of carbonyls, the range of accessible photocatalysts that meet the redox properties that match with the corresponding carbonyls is limited.

Organic electrosynthesis has emerged as a unique and irreplaceable tool for sustainable synthesis by employing electrons to circumvent the need for stoichiometric amounts of chemical redox agents.[2] Moreover, the direct electroreduction of carbonyls to the corresponding ketyl radicals obviates the use of expensive photocatalysts. As such, significant achievements toward the electrochemical generation of ketyl radicals have been made in the past decade. Since ketyl radicals are prone to homocoupling to afford pinacols, their employment in couplings with polarity-matched partners or other coupling partners in large molar excess are common strategies. In this graphical review, these electrochemical advancements are classified into three major categories: cross-pinacol couplings, coupling of carbonyls with alkyl radical precursors, and coupling of carbonyls with unsaturated systems (alkenes, alkynes, cyanoarenes, and heterocycles).

Figure 1 Electrochemical cross-pinacol coupling[3a] [b]

Figure 2 Electrochemical coupling of carbonyls with alkyl radical precursors[4`] [b] [c]

Figure 3 Electrochemical coupling of ketones with alkenes and alkynes[5`] [b] [c] [d] [e] [f] [g] [h]

Figure 4 Electrochemical coupling of carbonyls with cyanoarenes[6a] [b]

Figure 5 Electrochemical coupling of carbonyls with N-heterocycles[7`] [b] [c] [d]

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

We are grateful to Dr. Fantao Meng at BJUT for helpful discussions.

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Publication History

Received: 28 January 2024

Accepted after revision: 01 March 2024

Accepted Manuscript online:
01 March 2024

Article published online:
18 March 2024