Modern Electrochemical Aspects for the Synthesis of Value‐Added Organic Products

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 impo…

Innenrücktitelbild: Metall- und reagensfreie dehydrierende formale Benzyl-Aryl-Kreuzkupplung durch anodische Aktivierung in 1,1,1,3,3,3-Hexafluorpropan-2-ol (Angew. Chem. 37/2018)

Elektrifizierung der organischen Synthese

Einfache und doppelte metall- und reagensfreie anodische C-C-Kreuzkupplung von Phenolen mit Thiophenen

Erstmals ist es gelungen, eine elektrochemische dehydrierende C-C-Kreuzkupplung von Thiophenen mit Phenolen durchzufuhren. Diese nachhaltige und einfache anodische Kreuzkupplung eroffnet den Zugang zu zwei besonders interessanten Substanzklassen. Das Anwendungsgebiet der C-H-aktivierenden elektrochemischen Kreuzkupplung wurde dabei um Schwefelheterocyclen erweitert. Bisher konnten nur verschiedene benzoide aromatische Systeme umgesetzt werden, wohingegen die Verwendung von Heterocyclen bei der C-H-aktivierenden elektrochemischen Kreuzkupplung nicht erfolgreich war. In diesem Fall bieten reagens- und metallfreie Bedingungen einen nachhaltigen elektrochemischen Weg und damit einen vielverspre…

Selektive Synthese teilgeschützter unsymmetrischer Biphenole durch reagens‐ und metallfreie anodische Kreuzkupplung

Metal- and Reagent-Free Dehydrogenative Formal Benzyl-Aryl Cross-Coupling by Anodic Activation in 1,1,1,3,3,3-Hexafluoropropan-2-ol

A selective dehydrogenative electrochemical functionalization of benzylic positions that employs 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) has been developed. The electrogenerated products are versatile intermediates for subsequent functionalizations as they act as masked benzylic cations that can be easily activated. Herein, we report a sustainable, scalable, and reagent- and metal-free dehydrogenative formal benzyl-aryl cross-coupling. Liberation of the benzylic cation was accomplished through the use of acid. Valuable diarylmethanes are accessible in the presence of aromatic nucleophiles. The direct application of electricity enables a safe and environmentally benign chemical transformati…

Moderne Aspekte der Elektrochemie zur Synthese hochwertiger organischer Produkte

Selective Formation of 4,4'-Biphenols by Anodic Dehydrogenative Cross- and Homo-Coupling Reaction.

A simple and selective electrochemical synthesis by dehydrogenative coupling of unprotected 2,6- or 2,5-substituted phenols to the desired 4,4'-biphenols is reported. Using electricity as the oxidizing reagent avoids pre-functionalization of the starting materials, since a selective activation of the substrates takes place. Without the necessity for metal-catalysts or the use of stoichiometric reagents it is an economic and environmentally friendly transformation. The elaborated electrochemical protocol leads to a broad variety of the desired 4,4'-biphenols in a very simplified manner compared to classical approaches. This is particular the case for the cross-coupled products.

Selective Synthesis of Partially Protected Nonsymmetric Biphenols by Reagent‐ and Metal‐Free Anodic Cross‐Coupling Reaction

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…

Cover Picture: Source of Selectivity in Oxidative Cross-Coupling of Aryls by Solvent Effect of 1,1,1,3,3,3-Hexafluoropropan-2-ol (Chem. Eur. J. 35/2015)

ChemInform Abstract: Synthesis of meta-Terphenyl-2,2′′-diols by Anodic C-C Cross-Coupling Reactions.

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.

Source of Selectivity in Oxidative Cross-Coupling of Aryls by Solvent Effect of 1,1,1,3,3,3-Hexafluoropropan-2-ol

Abstract 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…

ChemInform Abstract: Source of Selectivity in Oxidative Cross-Coupling of Aryls by Solvent Effect of 1,1,1,3,3,3-Hexafluoropropan-2-ol.

Abstract 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…

Metall- und reagensfreie dehydrierende formale Benzyl-Aryl-Kreuzkupplung durch anodische Aktivierung in 1,1,1,3,3,3-Hexafluorpropan-2-ol

Synthesis ofmeta-Terphenyl-2,2′′-diols by Anodic C−C Cross-Coupling Reactions

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.

Synthese vonmeta-Terphenyl-2,2′′-diolen durch anodische C-C-Kreuzkupplungen

Die anodische C-C-Kreuzkupplung ist eine vielseitig einsetzbare Transformation, die eine gezielte Synthese von Biphenolen und arylierten Phenolen ermoglicht. Wir berichten uber einen ebenfalls elektrosynthetischen, metallfreien Ansatz, der einen Zugang zu symmetrischen und nichtsymmetrischen meta-Terphenyl-2,2′′-diolen in guten Ausbeuten und hoher Selektivitat ermoglicht. Symmetrische Derivate konnen durch eine direkte Synthese in einer ungeteilten Zelle gewonnen werden, wohingegen nichtsymmetrische meta-Terphenyl-2,2′′-diole zwei elektrochemische Stufen benotigen. Die milde Methode ist einfach durchzufuhren und skalierbar. Auserdem konnte erstmalig eine breite Substratvariabilitat aufgezei…

The Catalytic Effect of Fluoroalcohol Mixtures Depends on Domain Formation

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 l…

Inside Back Cover: Metal- and Reagent-Free Dehydrogenative Formal Benzyl-Aryl Cross-Coupling by Anodic Activation in 1,1,1,3,3,3-Hexafluoropropan-2-ol (Angew. Chem. Int. Ed. 37/2018)

A solvent-directed stereoselective and electrocatalytic synthesis of diisoeugenol.

A stereoselective and electrocatalytic coupling reaction of isoeugenol has been reported for the first time in a 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)/boron-doped diamond (BDD) electrode system. This particular C-C bond formation and diastereoselectivity is driven by a solvate interaction between the radical species and another isoeugenol molecule. Due to an electrocatalytic cycle, only understoichiometric amounts of charge are necessary. Since electric current is directly employed as the oxidant, the reaction is metal and reagent-free. In addition, the electrolysis can be conducted in a very simple undivided beaker-type cell under constant current conditions. Therefore, the protocol is …

Unexpected high robustness of electrochemical cross-coupling for a broad range of current density

Solvent effect enables electrosynthesis of organic compounds with strong variation of electric current at constant efficacy.

Cover Picture: Selective Synthesis of Partially Protected Nonsymmetric Biphenols by Reagent‐ and Metal‐Free Anodic Cross‐Coupling Reaction (Angew. Chem. Int. Ed. 39/2016)

Titelbild: Selektive Synthese teilgeschützter unsymmetrischer Biphenole durch reagens‐ und metallfreie anodische Kreuzkupplung (Angew. Chem. 39/2016)

Single and Twofold Metal- and Reagent-Free Anodic C-C Cross-Coupling of Phenols with Thiophenes.

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 …

Electrifying Organic Synthesis

Abstract 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 synth…

ChemInform Abstract: Selective Synthesis of Partially Protected Nonsymmetric Biphenols by Reagent- and Metal-Free Anodic Cross-Coupling Reaction.

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…

CCDC 1485994: Experimental Crystal Structure Determination

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CCDC 1840041: Experimental Crystal Structure Determination

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CCDC 1569308: Experimental Crystal Structure Determination

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CCDC 1476308: Experimental Crystal Structure Determination

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CCDC 1485996: Experimental Crystal Structure Determination

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CCDC 1858697: Experimental Crystal Structure Determination

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CCDC 1476309: Experimental Crystal Structure Determination

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CCDC 1008816: Experimental Crystal Structure Determination

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CCDC 1008819: Experimental Crystal Structure Determination

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CCDC 1485995: Experimental Crystal Structure Determination

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CCDC 1008820: Experimental Crystal Structure Determination

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CCDC 1569307: Experimental Crystal Structure Determination

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CCDC 1008818: Experimental Crystal Structure Determination

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CCDC 1008817: Experimental Crystal Structure Determination

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CCDC 1858698: Experimental Crystal Structure Determination

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CCDC 1840040: Experimental Crystal Structure Determination

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