Electroorganic synthesis has become an established, useful, and environmentally benign alternative to classic organic synthesis for the oxidation or the reduction of organic compounds. In this context, the use of redox mediators to achieve indirect processes is attaining increased significance, since it offers many advantages compared to a direct electrolysis. Kinetic inhibitions that are associated with the electron transfer at the electrode/electrolyte interface, for example, can be eliminated and higher or totally different selectivity can be achieved. In many cases, a mediated electron transfer can occur against a potential gradient, meaning that lower potentials are needed, reducing the probability of undesired side-reactions. In addition, the use of electron transfer mediators can help to avoid electrode passivation resulting from polymer film formation on the electrode surface. Although the principle of indirect electrolysis was established many years ago, new, exciting and useful developments continue to be made. In recent years, several new types of redox mediators have been designed and examined, a process that can be accomplished more efficiently and purposefully using modern computational tools. New protocols including, the development of double mediatory systems in biphasic media, enantioselective mediation and heterogeneous electrocatalysis using immobilized mediators have been established. Furthermore, the understanding of mediated electron transfer reaction mechanisms has advanced. This review describes progress in the field of electroorganic synthesis and summarizes recent advances.

Redox catalysis in organic electrosynthesis: basic principles and recent developments.

While preparative electrolysis of organic molecules has been an active area of research over the past century, modern synthetic chemists have generally been reluctant to adopt this technology. In fact, electrochemical methods possess many benefits over traditional reagent-based transformations, such as high functional group tolerance, mild conditions, and innate scalability and sustainability. In this Outlook we highlight illustrative examples of electrochemical reactions in the context of the synthesis of complex molecules, showcasing the intrinsic benefits of electrochemical reactions versus traditional reagent-based approaches. Our hope is that this field will soon see widespread adoption in the synthetic community.

https://pubsdc3.acs.org/doi/pdf/10.1021/acscentsci.6b00091

Synthetic Organic Electrochemistry: An Enabling and Innately Sustainable Method

Conventional methods for carrying out carbon–hydrogen functionalization and carbon–nitrogen bond formation are typically conducted at elevated temperatures, and rely on expensive catalysts as well as the use of stoichiometric, and perhaps toxic, oxidants. In this regard, electrochemical synthesis has recently been recognized as a sustainable and scalable strategy for the construction of challenging carbon–carbon and carbon–heteroatom bonds. Here, electrosynthesis has proven to be an environmentally benign, highly effective and versatile platform for achieving a wide range of nonclassical bond disconnections via generation of radical intermediates under mild reaction conditions. This review provides an overview on the use of anodic electrochemical methods for expediting the development of carbon–hydrogen functionalization and carbon–nitrogen bond formation strategies. Emphasis is placed on methodology development and mechanistic insight and aims to provide inspiration for future synthetic applications in the field of electrosynthesis.

/pdf/electrochemical-strategies-for-c-h-functionalization-and-c-n-13193n0ty2.pdf

Electrochemical strategies for C-H functionalization and C-N bond formation.

N-Oxyl compounds represent a diverse group of reagents that find widespread use as catalysts for the selective oxidation of organic molecules in both laboratory and industrial applications. While turnover of N-oxyl catalysts in oxidation reactions may be accomplished with a variety of stoichiometric oxidants, N-oxyl reagents have also been extensively used as catalysts under electrochemical conditions in the absence of chemical oxidants. Several classes of N-oxyl compounds undergo facile redox reactions at electrode surfaces, enabling them to mediate a wide range of electrosynthetic reactions. Electrochemical studies also provide insights into the structural properties and mechanisms of chemical and electrochemical catalysis by N-oxyl compounds. This review provides a comprehensive survey of the electrochemical properties and electrocatalytic applications of aminoxyls, imidoxyls, and related reagents, of which the two prototypical and widely used examples are 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) a...

Tetramethylpiperidine N-Oxyl (TEMPO), Phthalimide N-Oxyl (PINO), and Related N-Oxyl Species: Electrochemical Properties and Their Use in Electrocatalytic Reactions.

While organic electrochemistry can look quite different to a chemist not familiar with the technique, the reactions are at their core organic reactions. As such, they are developed and optimized using the same physical organic chemistry principles employed during the development of any other organic reaction. Certainly, the electron transfer that triggers the reactions can require a consideration of new “wrinkles” to those principles, but those considerations are typically minimal relative to the more traditional approaches needed to manipulate the pathways available to the reactive intermediates formed downstream of that electron transfer. In this review, three very different synthetic challenges—the generation and trapping of radical cations, the development of site-selective reactions on microelectrode arrays, and the optimization of current in a paired electrolysis—are used to illustrate this point.

Using Physical Organic Chemistry To Shape the Course of Electrochemical Reactions.

Alkaline salts of aci-forms of secondary nitro compounds, viz., β-nitropropylbenzene, nitrocyclohexane, 5-nitroheptan-2-one, and methyl-4-nitrohexanoate, were selectively or predominately oxidized into the corresponding ketones and their ketals under conditions of undivided amperostatic electrolysis in methanol. Mixtures of the corresponding aldehydes, their acetals, and methyl carboxylates were formed under similar conditions from the salts of primary nitro compounds, viz., 1-nitrohexane, nitromethylbenzene, and β-nitroethylbenzene.

Electrooxidative transformation of unsubstituted and substituted nitro hydrocarbons into carbonyl compounds

A new property of geminal bishydroperoxide was discovered: the ability to hydrolyze in acid medium in the presence of hydrogen peroxide with the formation of ketones. The most resistant to hydrolysis are the cyclic C6-bishydroperoxydes: at room temperature within one day they are practically not hydrolyzed; less stable is bishydroperoxycycloheptane (C7): in a day its one fifth part is hydrolyzed. Bishydroperoxydes with the cycles of C8 and C12 for the same time hydrolyzed to 80 and 90% respectively. Of the two linear bishydroperoxydes, 2,2-dihydroperoxydecane, with sterically unhindered center, is more resistant to hydrolysis than 6,6-dihydroperoxyundecane.

https://link.springer.com/content/pdf/10.1134/S1070363210080165.pdf

A new property of geminal bishydroperoxides: Hydrolysis with the removal of hydroperoxide groups to form a ketone

Electrolysis of 2-oxa- and 2,5-dioxabicyclo[n.4.0]alk-1(6)0enes (n=4, 10) under conditions of direct undivided anodic oxidation in methanol results in their electrochemical mono-and dimethoxylation; electrolysis of the corresponding 2-oxa-and 2,5-dioxabicycloalkanes involves electrochemical cleavage of the bridging carbon—carbon bonds followed by electrooxidative transformation into methyl ω-(2-methoxytetrahydrofuryl)-, ω-(dimethoxy-methyl)-, and ω-(1,3-dioxolan-2-yl)alkanoates.

Electrochemical transformations of monooxa- and dioxabicycloalkenes and -bicycloalkanes*

Electrochemical cleavage of a benzylic C-C bond in arylaliphatic compounds and the effect of the structure of their alkyl and aryl fragments on the process are studied. Cleavage was found to be the most effective for substituted benzenes and anisoles with side chains bearing vicinal methoxy- and hydroxy-groups in the a- and β-positions. Cleavage was moderate for cior β-methoxy(hydroxy)- and (β,β-dialkoxyalkyl)arenes. Electrolysis carried out in methanol results in formation of PhCH2OMe and PhCH(OMe)2 from PhCH2R and PhCH(OMe)R, benzaldehyde from (1,2-dihydroxypropyl)benzene, acetophenone from 2-phenylhexan-2-ol, 4-MeOC6H4CH(OMe)2 from 4-(1,2-dimethoxypropyl)anisole, and 2-(MeO)2CHC6H4CH(OMe)2 from 1,2-dimethoxyindan.

Electrochemical cleavage of a benzylic C--C bond in arylaliphatic compounds

A catalytic procedure has been developed for the synthesis of 15-pentadecanolide (1) from readily available 1-hydroperoxy-16-oxabicyclo[10.4.0]hexadecane (2). The method is based on the reaction of hydroperoxide2 with copper acetate (0.15–5 mol.%). Ring expansion occurred as a result of generation of tertiary bicyclohexadecyloxyl radicals4 from hydroperoxide2 under the action of Cu1 ions, β-scission of the radicals accompanied by regioselective cleavage of the bridge bond to form macrocyclic C-centered radicals5, and their oxidation by Cu11 ions to (E)-11- and (E)-12-pentadecen-15-olides (6). The products obtained were converted into 15-pentadecanolide by subsequent catalytic hydrogenation over a Pd catalyst in a yield of more than 90% with respect to hydroperoxide2.

Yu. N. Ogibin

Papers

Electrooxidative transformation of unsubstituted and substituted nitro hydrocarbons into carbonyl compounds

A new property of geminal bishydroperoxides: Hydrolysis with the removal of hydroperoxide groups to form a ketone

Electrochemical transformations of monooxa- and dioxabicycloalkenes and -bicycloalkanes*

Electrochemical cleavage of a benzylic C--C bond in arylaliphatic compounds

Ring-expansion reaction of 1-hydroperoxy-16-oxabicyclo[10.4.0]hexadecane catalyzed by copper ions: use in the synthesis of 15-pentadecanolide