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.
The use of electricity instead of stoichiometric amounts of oxidizers or reducing agents in synthesis is very appealing for economic and ecological reasons, and represents a major driving force for research efforts in this area. To use electron transfer at the electrode for a successful transformation in organic synthesis, the intermediate radical (cation/anion) has to be stabilized. Its combination with other approaches in organic chemistry or concepts of contemporary synthesis allows the establishment of powerful synthetic methods. The aim in the 21st Century will be to use as little fossil carbon as possible and, for this reason, the use of renewable sources is becoming increasingly important. The direct conversion of renewables, which have previously mainly been incinerated, is of increasing interest. This Review surveys many of the recent seminal important developments which will determine the future of this dynamic emerging field.
Solvents such as 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) with a high capacity for donating hydrogen bonds generate solvates that enter into selective cross-coupling reactions of aryls upon oxidation. When electric current is employed for oxidation, reagent effects can be excluded and a decoupling of nucleophilicity from oxidation potential can be achieved. The addition of water or methanol to the electrolyte allows a shift of oxidation potentials in a specific range, creating suitable systems for selective anodic cross-coupling reactions. The shift in the redox potentials depends on the substitution pattern of the substrate employed. The concept has been expanded from arene-phenol to phenol-phenol as well as phenol-aniline cross-coupling. This driving force for selectivity in oxidative coupling might also explain previous findings using HFIP and hypervalent iodine reagents.
In
the present contribution, we investigated catalytically active
mixtures of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and aqueous H2O2 by molecular dynamics simulations. It is clearly
observable that the HFIP molecule strongly binds to the H2O2, which is necessary for the desired catalytic reaction
to occur. Upon the addition of the substrate cyclooctene to the solution,
this interaction is enhanced, which suggests that the catalytic activity
is increased by the presence of the hydrocarbon. We could clearly
observe the microheterogeneous structure of the mixture, which is
the result of the separation of the hydroxyl groups, water, and H2O2 from the fluorinated alkyl moiety in the form
of large domains, which span through large areas of the system. The
hydrocarbon, however, does not fit into either one of these two microphases,
and it forms separate aggregates in the macroscopically homogeneous
liquid, creating thereby a triphilic mixture. The latter kinds of
aggregates are mostly surrounded by the fluorous moieties, and therefore,
the H2O2 has to move from the polar through
the fluorous domain to be able to react with the cyclooctene. Accordingly,
the present reaction should be described figuratively as a phase transfer
or an interfacial reaction, rather than a homogeneous liquid-phase
process.
The oxidative cross-coupling of aromatic substrates without the necessity of leaving groups or catalysts is described. The selective formation of partially protected nonsymmetric 2,2'-biphenols via electroorganic synthesis was accomplished with a high yield of isolated product. Since electric current is employed as the terminal oxidant, the reaction is reagent-free; no reagent waste is generated as only electrons are involved. The reaction is conducted in an undivided cell, and is suitable for scale-up and inherently safe. The implementation of O-silyl-protected phenols in this transformation results in both significantly enhanced yields and higher selectivity for the desired nonsymmetric 2,2'-biphenols. The use of a bulky silyl group to block one hydroxyl moiety makes the final product less prone to oxidation. Furthermore, the partially silyl-protected 2,2'-biphenols are versatile building blocks that usually require tedious or low-yielding synthetic pathways. Additionally, this strategy facilitates a large variety of new substrate combinations for oxidative cross-coupling reactions.
The first electrochemical dehydrogenative C-C cross-coupling of thiophenes with phenols has been realized. This sustainable and very simple to perform anodic coupling reaction enables access to two classes of compounds of significant interest. The scope for electrochemical C-H-activating cross-coupling reactions was expanded to sulfur heterocycles. Previously, only various benzoid aromatic systems could be converted, while the application of heterocycles was not successful in the electrochemical C-H-activating cross-coupling reaction. Here, reagent- and metal-free reaction conditions offer a sustainable electrochemical pathway that provides an attractive synthetic method to a broad variety of bi- and terarylic products based on thiophenes and phenols. This method is easy to conduct in an undivided cell, is scalable, and is inherently safe. The resulting products offer applications in electronic materials or as [OSO] pincer-type ligands.
The anodic C-C cross-coupling reaction is a versatile synthetic approach to symmetric and non-symmetric biphenols and arylated phenols. We herein present a metal-free electrosynthetic method that provides access to symmetric and non-symmetric meta-terphenyl-2,2''-diols in good yields and high selectivity. Symmetric derivatives can be obtained by direct electrolysis in an undivided cell. The synthesis of non-symmetric meta-terphenyl-2,2''-diols required two electrochemical steps. The reactions are easy to conduct and scalable. The method also features a broad substrate scope, and a large variety of functional groups are tolerated. The target molecules may serve as [OCO](3-) pincer ligands.
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