Electrophilic versus nucleophilic

FIGURE 13.4 Electrophilicity versus nucleophilicity (value of to- times 10). (Reprinted from De Vleeschouwer, F., Van Speybroeck, V., Waroquier, M., Geerlings, P., and DeProft, F., Org. Lett., 9, 2721, 2007. With permission.)... 

In summary, then, the diradical versus zwitterionic issue seems to have shifted in recent years, away from an either/or dichotomy and toward a more integrated view, one seeing tetramethylene intermediates as more or less dipolar diradicals. A small amount of zwitterionic character does not obviate the essentially diradical nature of these intermediates, any more than monoradicals forego radical character if they are more or less electrophilic or nucleophilic. 

So far, catalyst design has aimed mainly at oxidant activation and little attention has been paid to the interaction between the metal center and the alkene. A requirement for a successful epoxidation system of wide scope for simple terminal alkenes would seem to be a new catalyst design focusing on activation of the substrate instead of the oxidant. This suggests noble metals as applicable catalytic centers, because of their affinity for terminal alkenes versus internal ones. This results in a change of role for the catalyst from electrophile to nucleophile in the system. 

AT-heterocyclic carbenes show a pure donor nature. Comparing them to other monodentate ligands such as phosphines and amines on several metal-carbonyl complexes showed the significantly increased donor capacity relative to phosphines, even to trialkylphosphines, while the 7r-acceptor capability of the NHCs is in the order of those of nitriles and pyridine [29]. This was used to synthesize the metathesis catalysts discussed in the next section. Experimental evidence comes from the fact that it has been shown for several metals that an exchange of phosphines versus NHCs proceeds rapidly and without the need of an excess quantity of the NHC. X-ray structures of the NHC complexes show exceptionally long metal-carbon bonds indicating a different type of bond compared to the Schrock-type carbene double bond. As a result, the reactivity of these NHC complexes is also unique. They are relatively resistant towards an attack by nucleophiles and electrophiles at the divalent carbon atom. 

While its precise role remains unclear, the catalyst 3m is supposed not only to activate the electrophile (26), but also to lower the nucleophilicity of the amide nitrogen atom (Fig. 5). The latter interaction may account for a chemoselective Friedel-Crafts-type alkylation versus an aza-Darzens reaction. 

This crucial difference, that is, the formation of a more electrophilic species versus that of a strong nucleophile, is ultimately responsible for the observed difference in activity. 

The radical versus electrophilic character of triplet and singlet carbenes also shows up in relative reactivity patterns shown in Table 10.1. The relative reactivity of singlet dibromocarbene toward alkenes is more similar to that of electrophiles (bromination, epoxidation) than to that of radicals ( CC13). Carbene reactivity is strongly affected by substituents.61 Various singlet carbenes have been characterized as nucleophilic, ambi-philic, and electrophilic as shown in Table 10.2. This classification is based on relative reactivity toward a series of different alkenes containing both nucleophilic alkenes, such as tetramethylethylene, and electrophilic ones, such as acrylonitrile. The principal structural feature that determines the reactivity of the carbene is the ability of the substituents to act as electron donors. For example, dimethoxycarbene is devoid of electrophilicity toward... 

The complementary approach, activation of unsaturated hydrocarbons toward electrophilic attack by complexation with electron-rich metal fragments, has seen limited investigation. Although there are certainly opportunities in this area which have not been exploited, the electrophilic reactions present a more complex problem relative to nucleophilic addition. For example, consider the nucleophilic versus electrophilic addition to a terminal carbon of a saturated 18-electron metal-diene complex. Nucleophilic addition generates a stable 18-electron saturated ir-allyl complex. In contrast, electrophilic addition at carbon results in removal of two valence electrons from the metal and formation of an unstable ir-allyl unsaturated 16-electron complex (Scheme 1). 

Note again that 5 here differs from s in the Swain-Scott equation which refers to the slope of a plot of log k versus the nucleophilicity parameter n (or N) rather than electrophilicity parameter (E). 

Just as N for a nucleophile can be determined from a plot of log k against E for a series of electrophiles, in principle, the value of E for an electrophile can be determined from the intercept (at E + N = 0) of a plot of log (k/s) versus N for a series of nucleophiles (or indeed, if need be, from the measurement for a single nucleophile). In this way E values have been determined for many electrophiles other than benzhydryl cations, including metal-coordinated cations,186 BF3-coordinated aldehydes,274 tropylium ions, and many benzylic-and heteroatom-substituted carbocations. In the low reactivity range... 

Formation of a highly electrophilic iodonium species, transiently formed by treatment of an alkene with iodine, followed by intramolecular quenching with a nucleophile leads to iodocyclization. The use of iodine to form lactones has been elegantly developed. Bartlett and co-workers216 reported on what they described as thermodynamic versus kinetic control in the formation of lactones. Treatment of the alkenoic acid 158 (Scheme 46) with iodine in the presence of base afforded a preponderance of the kinetic product 159, whereas the same reaction in the absence of base afforded the thermodynamic product 160. This approach was used in the synthesis of serricorin. The idea of kinetic versus thermodynamic control of the reaction was first discussed in a paper by Bartlett and Myerson217 from 1978. It was reasoned that in the absence of base, thermodynamic control could be achieved in that a proton was available to allow equilibration to the most stable ester. In the absence of such a proton, for example by addition of base, this equilibration is not possible, and the kinetic product is favored. 

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