Nucleophile-electrophile electron transfer

With saturated electrophiles [n-BuBr, Eq. (1.43)] die SET is to a less nucleophilic leaving group [N - + R X (E) - N R + X . The driving force for nucleophile-electrophile electron-transfer reactions is the redox potential for the nucleophile in the solution matrix (HO-/HO-, +0.92 V vs. NHE in MeCN)42 plus the nucleophile-substrate bond-formation free energy (—AGBF, n-Bu—OH 349 kJ mol-1) ... 

The equation does not take into account such pertubation factors as steric effects, solvent effects, and ion-pair formation. These factors, however, may be neglected when experiments are carried out in the same solvent at the same temperature and concentration for an homogeneous set of substrates. So, for a given ambident nucleophile the rate ratio kj/kj will depend on A and B, which vary with (a) the attacked electrophilic center, (b) the solvent, and (c) the counterpart cationic species of the anion. The important point in this kind of study is to change only one parameter at a time. This simple rule has not always been followed, and little systematic work has been done in this field (12) stiH widely open after the discovery of the role played by single electron transfer mechanism in ambident reactivity (1689). 

Backside attack may be favored in order to facilitate transfer of nonbonding electrons from the nucleophile into the electrophile s lowest-unoccupied molecular orbital (LUMO). Efficient electron transfer requires maximal overlap of the LUMO and the donor orbital (usually a nonbonded electron pair on the nucleophile). Examine the LUMO of methyl bromide. How would a nucleophile have to approach in order to obtain the best overlap Is your answer more consistent with preferential backside or frontside attack ... 

Apply the same analysis to trimethyloxonium ion, MesO" a cationic electrophile. Examine the LUMO. What are the best sites for nucleophile-LUMO overlap How would electron transfer affect CO bond lengths ... 

The electrophilic character of sulfur dioxide does not only enable addition to reactive nucleophiles, but also to electrons forming sulfur dioxide radical anions which possess the requirements of a captodative" stabilization (equation 83). This electron transfer occurs electrochemically or chemically under Leuckart-Wallach conditions (formic acid/tertiary amine - , by reduction of sulfur dioxide with l-benzyl-1,4-dihydronicotinamide or with Rongalite The radical anion behaves as an efficient nucleophile and affords the generation of sulfones with alkyl halides " and Michael-acceptor olefins (equations 84 and 85). 

Electron donors (D) and electron acceptors (A) constitute reactant pairs that are traditionally considered with more specific connotations in mind - such as nucleophile/electrophile in bond formation, reductant/oxidant in electron transfer, base/acid in adduct production, and so on. In each case, the chemical transformation is preceded by a rapid (diffusion-controlled) association to form the 1 1 intermolecular complex9 (equation 2). 

The electron-transfer paradigm for chemical reactivity in Scheme 1 (equation 8) provides a unifying mechanistic basis for various bimolecular reactions via the identification of nucleophiles as electron donors and electrophiles as electron acceptors according to Chart 1. Such a reclassification of either a nucleophile/ electrophile, an anion/cation, a base/acid, or a reductant/oxidant pair under a single donor/acceptor rubric offers a number of advantages previously unavailable, foremost of which is the quantitative prediction of reaction rates by invoking the FERET in equation (104). 

Synthetic organic chemistry applications employing alkane C-H functionalizations are now well established. For example, alkanes can be oxidized to alkyl halides and alcohols by the Shilov system employing electrophilic platinum salts. Much of the Pt(ll)/Pt(rv) alkane activation chemistry discussed earlier has been based on Shilov chemistry. The mechanism has been investigated and is thought to involve the formation of a platinum(ll) alkyl complex, possibly via a (T-complex. The Pt(ll) complex is oxidized to Pt(iv) by electron transfer, and nucleophilic attack on the Pt(iv) intermediate yields the alkyl chloride or alcohol as well as regenerates the Pt(n) catalyst. This process is catalytic in Pt(ll), although a stoichiometric Pt(rv) oxidant is often required (Scheme 6).27,27l 2711... 

Each of the reactants (A and B) can be classified as electrophilic or nucleophilic by evaluating the energy cost for an electron transfer from A to B, described by the... 

When a molecule accepts electrons, the electrons tend to go to places where/1 (r) is large because it is at these locations that the molecule is most able to stabilize additional electrons. Therefore a molecule is susceptible to nucleophilic attack at sites where/ "(r) is large. Similarly, a molecule is susceptible to electrophilic attack at sites where f (r) is large, because these are the regions where electron removal destabilizes the molecule the least. In chemical density functional theory (DFT), the Fukui functions are the key regioselectivity indicators for electron-transfer controlled reactions. 

When the nucleophile is an electron-rich molecule, RC60+ can be reduced via single electron transfer, producing a dimer (47). Thus, electrophilic aromatic substitution normally occurs with substituted benzenes (Figure 22, [A]), but the mode of the reaction is switched if the benzene is strongly activated (Figure 22, [B]). 

A first turning point in the dichotomy between radical and ionic chemistry is located at the level of the primary radical, usually an ion radical, formed upon single electron transfer to the substrate. If, for a reduction, the reaction medium is not too acidic (or electrophilic), and for an oxidation, not too basic (or nucleophilic), radical reactions involving the primary radical, such as self-coupling, have a first opportunity to compete successfully with acid-base reactions. In this competition, the acidity (for a reduction) or basicity (for an oxidation) of the substrate should also be taken into account insofar as they may lead to father-son acid-base reactions. It should also be taken into consideration that the primary radical may undergo spontaneous acid-base reactions such as expelling a base (or a nucleophile) after a reduction, and an acid (or an electrophile) after an oxidation. 

Finally, we ask, if the reactive triads in Schemes 1 and 19 are common to both electrophilic and charge-transfer nitration, why is the nucleophilic pathway (k 2) apparently not pertinent to the electrophilic activation of toluene and anisole One obvious answer is that the electrophilic nitration of these less reactive [class (ii)] arenes proceeds via a different mechanism, in which N02 is directly transferred from V-nitropyridinium ion in a single step, without the intermediacy of the reactive triad, since such an activation process relates to the more conventional view of electrophilic aromatic substitution. However, the concerted mechanism for toluene, anisole, mesitylene, t-butylbenzene, etc., does not readily accommodate the three unique facets that relate charge-transfer directly to electrophilic nitration, viz., the lutidine syndrome, the added N02 effect, and the TFA neutralization (of Py). Accordingly, let us return to Schemes 10 and 19, and inquire into the nature of thermal (adiabatic) electron transfer in (87) vis-a-vis the (vertical) charge-transfer in (62). 

These alkylations can be looked upon as aliphatic nucleophilic substitutions, usually thoughtto proceed via SnI, Sn2, or hybrids of these mechanisms. However, in recent years more and more evidence for a single-electron transfer (SET) mechanism, represented in Eqs. (28-31), was obtained, and it was suggested that Sn2 and SET are just limiting cases of the same single-electron transfer mechanism [205, 206]. The S ET pathway involves first a transfer of an electron from the nucleophile to the electrophile followed by bond formation, whereas the Sn2 reaction involves a... 

An inner-sphere electron reduction has been proposed as a possible mechanism for the Fe(II)-induced decomposition of 1,2,4-trioxolanes (ozonides) (75) and (76). Benzoic acid was found to be the major product. The nucleophilic Ee(II) species attack the ozonide from the less hindered side of the electrophilic 0-0 a orbital to generate exclusively the Ee(III) oxy-complexed radical (inner-sphere electron transfer). After selective scission of the C-C bond, the resulting carbon-centred radical produced the observed product. The substituent effect determine the regioselective generation of one of the two possible Fe(III)-complexed oxy radicals. The bond scission shown will occur if R is bulkier than R. ... 

The inner salt (93) is able to react with both electrophiles (RI) and nucleophiles (RM) to give (92) and (94), respectively. Radical combination following single electron transfer from the nucleophile is believed to account for the thiophilic addition whereby the negatively charged nucleophile fails to react at the positively charged carbenium carbon. 

Ion-radical organic reactions of the Sj j l type are less sterically restricted than classical Sj reactions. Generally, the nucleophilic (not Sj j ) reactivity varies with the steric demand at the reaction center. The electron-transfer reactivity does not depend on steric effects. To illustrate this, one can compare electron transfer and nucleophilic reactivity between ketene silyl acetals and cationic electrophiles (Fukuzumi et al. 2001). Nevertheless, space strains may determine the overall results of these reactions if either intermediate radicals or forming products are sterically hindered. 

Nucleophilic and electrophilic substitutions in anion- and cation-radical, respectively, have been considered throughout the book, including the problem of a choice between addition and electron-transfer reactions. Therefore, only some unusual cases are discussed here. 

In addition to simple electron transfers in which no chemical bond is either broken or formed, numerous organic reactions, previously formulated by movements of electron pairs, are now understood as processes in which an initial electron transfer from a nucleophile (reductant) to an electrophile (oxidant) produces a radical ion pair, which leads to the final products via the follow-up steps involving cleavage and formation of chemical bonds [11-23], The follow-up steps are usually sufficiendy rapid to render the initial electron transfer the rate-determining step in an overall irreversible transformation [24], In such a case, the overall reactivity is determined by the initial electron-transfer step, which can also be well designed based on the redox potentials and the reorganization energies of a nucleophile (reductant) and an electrophile (oxidant). 

The first intermediate to be generated from a conjugated system by electron transfer is the radical-cation by oxidation or the radical-anion by reduction. Spectroscopic techniques have been extensively employed to demonstrate the existance of these often short-lived intermediates. The life-times of these intermediates are longer in aprotic solvents and in the absence of nucleophiles and electrophiles. Electron spin resonance spectroscopy is useful for characterization of the free electron distribution in the radical-ion [53]. The electrochemical cell is placed within the resonance cavity of an esr spectrometer. This cell must be thin in order to decrease the loss of power due to absorption by the solvent and electrolyte. A steady state concentration of the radical-ion species is generated by application of a suitable working electrode potential so that this unpaired electron species can be characterised. The properties of radical-ions derived from different classes of conjugated substrates are discussed in appropriate chapters. 

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