Redox-umpolung

The principle of electrochemical redox- Umpolung has been uniquely applied in cyclization. Thereby, one of two donors in the acyclic precursor is oxidized to an acceptor, whose reaction with the donor leads to cyclization. The same holds for the cyclization by way of reduction of one out of two acceptors [15]. 

From the retrosynthetic point of view, electrochemical redox reactions are an easy way to accomplish the principle of redox-umpolung (polarity reversal) [2]. As can be seen in Scheme 22.1, oxidation of an electron-rich neutral compound will lead to an electrophilic cation radical, or starting with a nucleophilic anion, anodic oxidation may lead to an electrophilic cation. In the mirror image reductions, an electron-poor neutral compound is transformed to a nucleophilic anion radical, or an electrophilic cation will end up as a nucleophilic anion. 

Electrophilic reactions on the electron-deficient anthraquinone are normally not possible. However, in 1936 Marschalk described the facile alkylation of the anthraquinone nucleus by aldehydes after reduction of the quinone to the electron-rich hydroquinone using dithionite [34]. This strategy might be called a redox Umpolung , since the chemical reactivity of the anthracene core is reversed by the redox reaction. 

Single electron oxidation of the non-activated carbonyl group, e.g. in aliphatic or aromatic aldehydes, ketones and carboxylic acid derivatives, is, on the other hand, much less feasible and only a handful of methods and synthetic applications are known. Useful methods for synthetic applications are chemical modifications to lower the oxidation potentials by peripheral donor substitution and a-silylation, or redox umpolung via oxidation of the corresponding carbonyl enols or enol ethers. 

An electrode is inexpensive when compared with most chemical reagents. It is immobile, and thus causes less environmental and solubility problems than most chemical oxidants and reductants. It can change the polarity of reagents by oxidation or reduction ( Redox-Umpolung ) and in this way can shorten synthetic sequences. Controlled potential electrolysis allows the selective conversion of one out of several electrophores in a molecule. A technical scale-up causes in most cases lesser problems than the scale-up of a chemical reaction. These advantages and the wide choice of conversions have made electrolysis today at least for those that take the small effort to assemble an electrolysis cell and connect it to a d.c. power supply - to an attractive alternative and supplement for chemical synthetic methods. 

Besides that, electrochemical methods can be used to activate aromatic substrates by means of redox-umpolung procedure, which makes possible to cOTivert imreactive arenes, azoles, phenols, and other aromatic compounds, bearing electron-donating groups, into the intermediate radical cation species, which are able to react with nucleophiles (Scheme 61) [47, 187]. 

The principle ways by which one can attain umpolung have been summarized in a comprehensive paper by Seebach [2]. One far-reaching principle in this context is redox-umpolung. An a-synthon may be converted into a d-synthon simply by the addition of two electrons (2e-reduction) in reverse, a d-synthon is converted into an a-synthon by a two-electron oxidation (Scheme 2.15). 

Redox-umpolung can be achieved under actual synthesis conditions. One limitation, though, arises from the fact that the d-synthon, for example, is generated via redox-umpolung in the presence of its precursor a-synthon. 

Scheme 2.16 Formation of symmetrical 1,2- and 1,6-difunctionalized skeletons by in situ redox-umpolung...

Stoichiometric redox-umpolung becomes possible when the electron transfer process is faster than any coupling step, i.e., when the tendency of both the a- and the d-synthon for coupling is low. A classical example of such a situation is Grignard formation from alkyl or aryl halides, where the coupling product is generally formed only as a minor side product (Scheme 2.17). 

Scheme 2.17 Stoichiometric redox-umpolung during the formation of Grignard reagents...

Heterocoupling of two different partners via in situ redox-umpolung is often synthetically more valuable than simple homocoupling. If, for two a-synthons, partner A is more readily reduced than partner B, and partner B is more reactive towards a d-synthon than partner A, then heterocoupling... 

Scheme 2.18 In situ redox-umpolung (direct or copper-mediated) resulting in heterocoupling products...

Intramolecular heterocoupling, i.e., ring closure via in situ redox-umpolung is achieved more readily than the intermolecular version because of favorable effectve concentration of the reacting partners (Scheme 2.19). 

One generally associates with redox-umpolung the removal or addition of two electrons, which results in the correct stoichiometry of the reagents to be employed. It is less well recognized, however, that removal or addition of just one electron is sufficient to cause umpolung in reactivity (Scheme 2.24). 

Another in situ umpolung that fits here is the one electron redox umpolung of P dicarbonyl compounds, mentioned on p. 22 and the related oxidation of enolates [63] or of enamines [64] (Scheme 2.42). 

Titanium A reductive cross-coupling of acrylonitriles CH2=CHCN with cyclo-hexenone and other enones, which connects the jS-carbons of both substrates, can be catalysed by Ti(III), generated from Cp2TiCl2 by reduction with zinc (in reminiscence of McMurry coupling). A plausible mechanism, involving a redox umpolung of the enone, has been proposed. " ... 

The second concept is to switch the reactivity of the complex by addition or substruction of one or two electrons to or from the complex applies the Umpolung principle. The effect of redox change is dramatic increase in the rate is often of the order of 109 for a given reaction [15-18]. These properties are summarized in the following Scheme I ... 

Keywords Benzoin Carbene NHC Nucleophihc Catalysis Organocatalysis Redox Stetter Transesterification Umpolung... 

The PAR is easy to apply, and the crucial need is only to identify correctly the donor or acceptor nature of a polar substituent. It should be mentioned that an interesting phenomenon called contrapolarization [8] can often be observed. This phenomenon pertains to a role change of an atomic center during a reaction step, it occurs ubiquitously in redox processes. Contrapolarization is unintentional and transitory umpolung. 

Redox condensation between two carbonyl groups by virtue of intramolecularity can be initiated by an azolecarbene. The more electrophilic formyl group that is attached to an aromatic ring undergoes umpolung by accepting the carbene/ylide then the adduct adds across a proximal carbonyl group. The use of a chiral carbene (e.g., 192) naturally empowers enan-tiomerization of the reaction. ... 

NHC-catalyzed reactions are unique in organic synthesis, and very useful for the construction of carbon-carbon bonds. Great success has been made for the NHC-catalyzed benzoin condensation, Stetter reactions, and a -d Umpolung reactions in the past decades. NHC catalysis has also hnd application in many other reactions, such as umpolung of Michael acceptors, Morita-Baylis-Hilman reaction, Michael additions, redox reaction, and reactions of ketenes. With the rapid development of NHC catalysis, more reactions will surely be found, and the wide applications in organic synthesis could be expected. 

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