Chem. Rev. 2008, 108, 2265–2299 2265 Modern Strategies in Electroorganic Synthesis Jun-ichi Yoshida,* Kazuhide Kataoka, Roberto Horcajada, and Aiichiro Nagaki Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan, and JST Innovation Plaza, Kyoto, Nishikyo-ku Kyoto 615-8245, Japan Received November 26, 2007 Contents 1. Introduction 2265 2. Background 2266 3. Intramolecular Control 2267 3.1. Electroauxiliaries 2267 3.1.1. Principles of Electroauxiliaries 2267 3.1.2. Applications of Electroauxiliaries 2271 3.1.3. Electroauxiliaries for Chemical and 2275 Photochemical Reactions 3.2. Template-Directed Methods 2276 4. Reaction Media 2276 4.1. Ionic Liquid 2276 4.1.1. Electrochemical Properties of Ionic Liquids 2277 4.1.2. Electrochemical Reactions in Ionic Liquids 2277 Jun-ichi Yoshida was born in Osaka, Japan in 1952. He graduated from Kyoto University in 1975, where he received his doctor’s degree under 4.1.3. Electrochemical Polymerization in Ionic 2280 the supervision of Prof. Makoto Kumada in 1981. In 1979 Yoshida joined Liquid the faculty at Kyoto Institute of Technology as an assistant professor. In 4.2. Solid-Supported Electrolytes 2280 the meantime, he visited University of Wisconsin during 1982-1983, where 4.3. Solid-Supported Mediators 2282 he joined the research group of Prof. B. M. Trost. In 1985 he moved to 4.4. Supported Substrate-Product Capture 2283 Osaka City University, where he was promoted to an associate professor in 1992. In 1994 he was appointed as a full professor of Kyoto University. 4.5. A Unique Electrolyte/Solvent System 2285 His research interests include integrated organic synthesis on the basis 5. Reaction Conditions 2285 of reactive intermediates, organic electron transfer reactions, organometallic 5.1. Supercritical Fluids 2285 reactions, and microreactors. Awards: the Progress Award of Synthetic Organic Chemistry, Japan (1987), the Chemical Society of Japan Award 5.1.1. Electrochemical Properties of scCO2 2285 for Creative Work (2001), Nagoya Silver Medal of Organic Chemistry 5.1.2. Electroreductive Carboxylation in scCO2 2286 (2006), and Humboldt Research Award (2007). 5.1.3. Electrochemical Polymerization in scCO2 2286 5.2. The Cation-Pool Method 2286 5.2.1. Generation of N-Acyliminium Ion Pools 2286 5.2.2. Generation of Alkoxycarbenium Ion Pools 2287 5.2.3. Generation of Diarylcarbenium Ion Pools 2288 5.2.4. Generation of Other Cation Pools 2289 6. Electrochemical Devices 2289 6.1. Electrode Materials 2289 6.2. Ultrasound and Centrifugal Fields 2290 6.3. Electrochemical Microflow Systems 2290 7. Combinatorial Electrochemical Synthesis 2292 7.1. Parallel Electrolysis Using a Macrosystem 2292 7.2. Parallel Electrolysis Using a Microsystem 2293 7.3. Serial Electrolysis Using a Microsystem 2294 8. Conclusions 2294 Kazuhide Kataoka was born in Okayama in 1977 and received his Ph.D. 9. Acknowledgments 2294 in 2005 under the direction of Professor J. Nokami from Okayama 10. References 2294 university of science. Thereafter, he moved to JST Innovation Plaza, Kyoto. His main research interests are electroorganic chemistry. 1. Introduction cess, one electron is added to or removed from a substrate molecule. Such an electron transfer is reversible only when Electron transfer is one of the most important processes the resulting species is stable under those conditions. In other in organic chemistry, and many organic reactions are driven cases, an electron transfer triggers subsequent chemical by electron-transfer processes.1 In an electron-transfer pro- processes, such as bond dissociation and bond formation. 10.1021/cr0680843 CCC: $71.00 2008 American Chemical Society Published on Web 06/20/2008 2266 Chemical Reviews, 2008, Vol. 108, No. 7 Yoshida et al. mild conditions. In fact, radical cations and radical anions can be generated by electrochemical electron-transfer reac- tions of neutral organic compounds. Carbocations, carbon free radicals, and carbanions can also be generated by subsequent bond-dissociation or bond-forming processes. These reactive carbon species are utilized in various synthetic transformations, especially carbon-carbon bond formations. Oxidation and reduction of functional groups are also important transformations in organic synthesis, and the electrochemical method serves as “greener” procedures for such transformations. Therefore, electroorganic synthesis3,4 has received significant research interest from both academia and industry. Because modern applications of traditional electrochemical 5 Roberto Horcajada studied the Degree in Chemistry at the University of methods have been recently reviewed, this article will Alcala de Henares in Spain, where he briefly collaborated with Prof. Barba provide an outline of principles and applications of new in the field of organic electrochemistry. Then he moved to the Queen methods for effecting organic electrochemical reactions that Mary University of London for his Ph.D. under the supervision of Prof. have been developed in recent decades. James H. P. Utley and Dr. Peter B. Wyatt in the field of Electrogenerated Chiral Bases. After a short period at the Institute of biotechnology with Prof. Elisabeth H. Hall, he joined the Department of Synthetic Chemistry 2. Background and Biological Chemistry of the University of Kyoto with Prof. Jun-ichi Yoshida for two years to develop, among other research projects, parts While extensive work has been done to control the of the present work. He is currently working at the Barcelona based selectivity of traditional chemical methods, less work has company IUCT as International Projects Coordinator, managing several been aimed at electrochemical methods. It is important to multimillion Euro projects. note that reactivity control of substrates at the molecular level has been rather neglected, although a full repertoire of methods for such control has been developed. For example, directing groups that coordinate metal centers and guide the course of reactions are very popular in organometallic synthesis,6 but a similar approach has not been widely used in electrochemical synthesis. This is an important gap because the electrochemical reaction offers unique challenges that cannot always be solved using methods employed in traditional chemical reactions. These challenges should involve controlling both the selectivity of electron transfer and the subsequent formation of reactive intermediates at the molecular level. A variety of new reaction media and separation methods such as solid-phase synthesis7 and strategic separation8 have been developed in modern organic synthesis. The use of Aiichiro Nagaki was born in Osaka, Japan, in 1973. He received his Ph.D. similar methods may open new possibilities of organic in 2005 from Kyoto University under the supervision of Professor Jun- ichi Yoshida. He worked with Professor Hiroaki Suga, Tokyo University, electrochemical synthesis, although a simple combination of for one year as a postdoctoral fellow. In 2006, he became an assistant a polar organic solvent and an ionic supporting electrolyte professor of Kyoto University and joined the research group of Professor has been commonly used in conventional organic electro- Jun-ichi Yoshida. In 2005, he received the Bulletin Chemical Society of chemistry. Japan Award in Synthetic Organic Chemistry, Japan. His current research interests are organic synthesis, electroorganic synthesis, and microreactor In modern organic synthesis, low temperatures and anhy- synthesis. drous conditions are often employed to conduct reactions in a highly selective manner. However, it has been considered In organic synthesis, electron-transfer-driven reactions that electrochemical reactions should be conducted at around have been widely used for various transformations, although room temperature and that the presence of moisture is their potential has not yet been fully utilized. Among several inevitable, although this is not the case any more if we choose methods for electron-transfer-driven reactions, the electro- an appropriate solvent/electrolyte system. The choice of chemical method serves as a straightforward and powerful method. In fact, various carbon-carbon bond formations and appropriate devices for electrolysis is also important, because functional group transformations can be accomplished by the cell conductivity and mass transfer on the surface of the electrochemical method. For example, the Kolbe reaction2 electrode are crucial for efficiency and selectivity of elec- that involves the oxidation of carboxylate anions at an anode trochemical reactions. Such issues might be a barrier to has been known for many years and still serves as a powerful applications of the electrochemical method in organic tool for carbon-carbon bond formation in organic synthesis. synthesis. In the Kolbe reaction, the initial electron transfer followed However, extensive studies have been carried out recently by the elimination of CO2 generates carbon free radicals, to solve such problems, and many different types of strategies which homocouple to make a new carbon-carbon bond. It have been reported in the literature. Such strategies, which is noteworthy that the electrochemical method serves as an will be discussed in the following sections, open up new excellent method for the generation of reactive species under possibilities for electroorganic synthesis. Modern Strategies in Electroorganic Synthesis Chemical Reviews, 2008, Vol. 108, No. 7 2267 straightforward