Umpolung reduction

A synthetically very potent and unique feature of organic electrosynthesis is the oxidative or reductive Umpolung of reactivity. Reactive acceptors are anodically available as radical cations in a wide variety by the oxidative Umpolung of donors. This way two donors can be coupled in one step if one of them is converted to an acceptor at the electrode. Chemically, at least two additional... 

Reactive donors can be generated ca-thodically by reductive cleavage of hahdes to carbanions or by reduction of double bonds to radical anions. Using these methods, two acceptors can be dimerized in one step by reductive Umpolung , for example, two molecules of acrylonitrile to adipodini-trile - a reaction, which normally needs two or more steps. 

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]. 

Reductive Umpolung of acyclic compounds with two acceptors allows efficient single-step cyclizations by converting one of the acceptors into a donor (Eq. 4) [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. 

Allylstannane 176 is formed by the reaction of allyl acetate with distannanes [97,98], In this reaction, umpolung of the electrophilic 7r-ally] palladium to the nucleophilic allylstannane occurs. Allylation of bromoindole 198 to give allylindole 199 involves the oxidative addition of 198 to Pd, transmetallation with the allylstannane 176, and final reductive elimination [99],... 

Umpolung of propargyl compounds occurs in the presence of excess Et2Zn, and homopropargyl alcohols 187 are obtained by the reaction of propargyl benzoates (186) with benzaldehyde, although the exact mechanism is not known. Ethylallene, which is expected to be formed by transmetallation of the allenylpalladium with Et2Zn and reductive elimination, is not formed [41],... 

The reductive lithiation of dioxolanes requires the formation of an allylic or benzylic organolithium, and represents a valuable umpolung method for the functionalisation of carbonyl compounds. 

Scheme 2. Sequence for the Umpolung Strategy -Reduction to the Group 1 (Ravidomycin) Substitution Pattern...

In the oxidative or reductive versions of the reaction types listed above the [nucleophile, electrophile] combination is not allowed instead we use [nucleophile, nucleophile] combinations oxidatively or [electrophile, electrophile] combinations reductively [R—E, Nu-], [C=C( J-), Nu-], [R—Nu, E+] and [C=C(<5+), E+]. This principle (Umpolung see Section 1) vastly increases the number of choices available for synthetic schemes, and particularly allows for short cuts in conventional ones. Thus, the synthesis of ArOH or ArCN from ArH normally requires four steps (18), whereas the... 

The bifunctional nature and the presence of a stereocenter make a-hydroxyketones (acyloins) amenable to further synthetic transformations. There are two classical chemical syntheses for these a-hydroxyketones the acyloin condensation and the benzoin condensation. In the acyloin condensation a new carbon-carbon bond is formed by a reduction, for instance with sodium. In the benzoin condensation the new carbon-carbon bond is formed with the help of an umpolung, induced by the formation of a cyanohydrin. A number of enzymes catalyze this type of reaction, and as might be expected, the reaction conditions are considerably milder [2-4, 26, 27]. In addition the enzymes such as benzaldehyde lyase (BAL) catalyze the formation of a new carbon-carbon bond enantioselectively. Transketolases (TK)... 

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. 

Most organometallic acceptors are positively charged complexes which show highly increased reduction potentials as compared to the isoelectronic neutral complexes. Several examples of such cationic organometallic acceptors (obtained by umpolung ) and their isoelectronic neutral counterparts which act as donors are summarized in Table 7. 

A carbonylation reaction with Ni(CO)4 generating 1,4,7-tricarbonyl compounds has also been published Synthesis of 1,6-dicarbonyl systems via mercury(II) intermediates and radical chain additions to electrophilic olefins has been achieved (equation 70). This sequence constitutes an umpolung if one considers that the carbonyl moiety is masked in siloxycyclopropanes TTireo-juvabione has been synthesized from a methoxycyclo-propane via a mercury(II) salt cleavage/reduction sequence ... 

Coenzymes and vitamins are Nature s versions of common organic reagents Reductions with NADH Reductive amination, deamination, and decarboxylation with pyridoxal Enol chemistry with lysine enamines, with coenzyme A, and with phosphoenolpyruvate Umpolung chemistry with thiamine as a d reagent... 

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. 

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