Umpolung effect

An interesting umpolung effect has been found in the alkylation of pyrroles with carbon nucleophiles via the endoperoxide (6.6)612). 

The current density has a dramatic influence on the yield of 52 and reveals that more than one electrode reaction is involved in the sequence. When the current density is in the range of 2.8. 7 mA/cm2, 52 is directly obtained in about 30% yield. The rationale for the formation of 52 starts with the direct or indirect generation of phenoxyl radicals at the BDD anode. Since the used conditions will provide concentrations of oxyl spin centers, which exclude a recombination, the transformation has to follow a different mechanistic course. The anodic treatment will cause an Umpolung effect because the electron rich phenol is oxidized [110-113]. Such phenoxyl species are still electrophilic despite the liberation of a proton [114-119]. The electrophilic attack occurs at the most electron rich position of the reaction partner which provides the observed connectivity in 52 (Scheme 21). 

A novel entry into these important intermediates is the anionic addition of the trimethylsilyl group, generated from 8, to acyl cyanides28. The final product is the result of an umpolung effect of the addition when the adduct, an a,/ -unsaturated acyl anion equivalent, adds to another molecule of acyl cyanide (equation 21). 

In the oxidative Eschenmoser sulfide contraction (Scheme 11), thioamide 59 is oxidized by benzoyl peroxide to give either a symmetrical disulfide or the O-benzoate of the thiolactam-S-oxide. In any event, the once-nucleophilic thioamide sulfur atom is now forced to adopt the role of electrophile a reactivity umpolung has, in effect, been achieved.13 The nucleophilic enamide 65 attacks the sulfur atom leading to the formation of sulfur-bridged intermediate 66. The action of a phosphine or a phosphite thiophile on the putative episulfide then gives vinylogous amidine 67. 

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 ... 

The attack of the nucleophile on the acceptor-substituted allene usually happens at the central sp-hybridized carbon atom. This holds true also if no nucleophilic addition but a nucleophilic substitution in terms of an SN2 reaction such as 181 — 182 occurs (Scheme 7.30) [245]. The addition of ethanol to the allene 183 is an exception [157]. In this case, the allene not only bears an acceptor but shows also the substructure of a vinyl ether. A change in the regioselectivity of the addition of nucleophilic compounds NuH to allenic esters can be effected by temporary introduction of a triphenylphosphonium group [246]. For instance, the ester 185 yields the phos-phonium salt 186, which may be converted further to the ether 187. Evidently, the triphenylphosphonium group induces an electrophilic character at the terminal carbon atom of 186 and this is used to produce 187, which is formally an abnormal product of the addition of methanol to the allene 185. This method of umpolung is also applicable to nucleophilic addition reactions to allenyl ketones in a modified procedure [246, 247]. 

The benzoin reaction dates back to 1832 when Wohler and Liebig reported that cyanide catalyzes the formation of benzoin 6 from benzaldehyde 5, a seminal example in which the normal mode of polarity of a functional group was reversed (Eq. 1) [26], This reversal of polarity, subsequently termed Umpolung [27], effectively changes an electrophilic aldehyde into a nucleophilic acyl anion equivalent. 

This reversal of polarity at an atom, which is referred to as an umpolung, cannot be effected directly on RCHO itself. The anion... 

The realization of the principle of umpolung , in which reactivity at a normally electrophilic site is inverted to that of a nucleophilic species,161 has resulted in the development of numerous masked acyl anion equivalents for carbon-carbon bond formation.162 The use of masked acyl anion equivalents for conjugate additions was made possible by several observations. First, Stork reported that protected cyanohydrins afforded preferential kinetic 1,4-addition with ot, 3-enonesl6b and second, Brown reported that preferential kinetic 1,4-addition of 1,3-dithianes was effected by the use of HMPA.163... 

Addition of the cyanide ion to create a cyanohydrin effects an umpolung of the normal carbonyl charge affinity, and the electrophilic aldehyde carbon becomes nucleophilic after deprotonation A thiazolium salt may also be used as the catalyst in this reaction. 

In this mode, an umpolung of reactivity for the nucleophile occurs, leading to many useful transformations. More complex pathways are not unusual these include addition to multiple bonds, vinylic and acetylenic substitution, rearrangements - some involving ring-expansion or ring-contraction - generation of reactive intermediates, etc. Solvent effects, especially solvent participation, may add new dimensions to reactivity. 

Redistribution of electron density in CT complexes results in a modification of the chemical properties of coordinated arenes, and this effect is widely used in organometallic catalysis [2]. To demonstrate the relationship between charge transfer in arene complexes and their reactivity, we focus our attention on carbon-hydrogen bond activation, nucleophilic/ electrophilic umpolung, and the donor/acceptor properties of arenes in a wide variety of organometallic reactions. 

The second major class of non-umpolung nucleophilic carbene catalysis comprises reactions by initial NHC-activation of various silicon compounds. Their proposed common pathway is thought to lead to a hypervalent silicon complex4 and thus provide carbene-catalyzed activation of the corresponding nucleophiles such as TMSCN, TMSCF3 etc. (Kano et al. 2006 Song et al. 2005 2006). It is not only certain carbon-silicon bonds that can be effectively activated, but a comparable activation of Si-O bonds, e.g. of trimethylsily enol ethers etc., allows for mild, NHC-promoted Mukaiyama aldol reactions (Scheme 6 Song et al. 2007). 

A way out may be found if the cycloaddition of diazomethane to 1 occurs in the reverse direction as represented in XVII. Now the newly introduced methylene will be in the appropriate position for ring expansion to a six-mem-bered ring. This requires that the first new C-C bond of I with diazomethane be formed at the /3 carbon of the cyano aciylate group as opposed to V. This is possible thanks to the inversion of polarity or umpolung of the double bond due to its conjugation with the nitrile. This effect along with the influence of the ester overrules the polarization pull of the lactam ring. 

A conceptually different entry into the preparation of dienolates and their use in vinylogous Mannich reactions was developed by Lautens and coworkers. Vinylox iranes can effectively be ring opened with catalytic amounts of a Lewis acid to furnish P,y unsaturated aldehydes that are in equilibrium with their dienol tautomer. As such this transformation involved an umpolung of the formerly electrophilic vinyl epoxide to the nucleophilic dienol that can be treated with electrophiles. 

The strategy of double umpolung appears suspect at first sight, but it has proven to be effective [86, 87] in the context of many demanding syntheses [88] (Scheme 2.50). 

Umpolung of anomeric effect A further extension of the anomeric effect has been used for C-Y donors and i-acceptors, where cyclohexanones, thiocyclohexanones, and methylenecyclohexanes benefit from... 

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