The direct synthetic organic use of electricity is currently experiencing a renaissance. More synthetically oriented laboratories working in this area are exploiting both novel and more traditional concepts, paving the way to broader applications of this niche technology. As only electrons serve as reagents, the generation of reagent waste is efficiently avoided. Moreover, stoichiometric reagents can be regenerated and allow a transformation to be conducted in an electrocatalytic fashion. However, the application of electroorganic transformations is more than minimizing the waste footprint, it rather gives rise to inherently safe processes, reduces the number of steps of many syntheses, allows for milder reaction conditions, provides alternative means to access desired structural entities, and creates intellectual property (IP) space. When the electricity originates from renewable resources, this surplus might be directly employed as a terminal oxidizing or reducing agent, providing an ultra-sustainable and therefore highly attractive technique. This Review surveys recent developments in electrochemical synthesis that will influence the future of this area.

Electrifying Organic Synthesis

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.

Elektrifizierung der organischen Synthese

Carboxylic acids can be decarboxylated by anodic oxidation to radicals (Kolbe-electrolysis) and/or carbocations (non-Kolbe electrolysis). The procedure and necessary equipment is simple, a scale-up easy, the choice of carboxylic acids wide, the selectivity towards radicals or carbocations can be controlled by reaction conditions and the structure of the carboxylic acid, the yields are in general good. The radical pathway can be used for the preparation of e.g. 1,n-diesters, pheromones, or rare fatty acids. Electrolysis in the presence of olefins affords additive dimers and monomers or by intramolecular addition five membered carbocycles and heterocycles. By non-Kolbe electrolysis carboxylic acids can be converted into ethers, acetals, olefins or acetamides. Rearrangements and fragmentations lead to stereospecifically substituted cyclopentanoids and one- or four-carbon ring extensions.

Recent Contributions of Kolbe Electrolysis to Organic Synthesis

Selective C-C bond cleavage under mild conditions can serve as a valuable tool for organic syntheses and macromolecular degradation. However, the conventional chemical methods have largely involved the use of noble transition-metal catalysts as well as the stoichiometric and perhaps environmentally unfriendly oxidants, compromising the overall sustainable nature of C-C transformation chemistry. In this regard, electrochemical C-C bond cleavage has been identified as a sustainable and scalable strategy that employs electricity to replace byproduct-generating chemical reagents. To date, the progress made in this area has mainly relied on Kolbe electrolysis and related processes. Encouragingly, more and more examples of the cleavage of C-C bonds via other maneuvers have recently been developed. This review provides an overview on the most recent and significant developments in electrochemically oxidative selective C-C bond cleavage, with an emphasis on both synthetic outcomes and reaction mechanisms, and it showcases the innate advantages and exciting potentials of electrochemical synthesis.

Helmut Klünenberg

Papers

Synthesis of Disparlure by Kolbe Electrolysis

A remarkable influence of the electrolyte in anodic cyclization of 1-benzyltetrahydroisoquinolins to neospirodienones or morphinandienones☆

Synthese von Disparlure durch Kolbe‐Elektrolyse