Intrinsic nucleophilicity

The second well-known electrophilicity or nucleophilicity scale was by Legon and Millen [13,14]. In this scale, the assigned intrinsic nucleophilicity is derived from the intermolecular stretching force constant k, recorded from the rotational and infrared (IR) spectra of the dimer B. .. HX formed by the nucleophile B and a series of HX species (for X halogens) and other neutral electrophiles. The nucleophilicity number in this case is obtained from the empirical relation... 

Intrinsic Nucleophilicity vs. Leaving Group Ability. As pointed out earlier, our definition of intrinsic nucleophilicity in terms of barriers to degenerate exchange reactions necessarily implies that nucleophilicity and leaving group ability are equivalent. This can be seen in either of two ways. First,... 

For further examples of the difficulty in assigning a reagent with an intrinsic nucleophilicity, see C. D. Ritchie, Accts. Ckem. Res., 5, 348 (1972). 

Most systematic studies on gas-phase SN2 reactions have been carried out with methyl halides, substrates which are free of complications due to competing elimination. Application of the Marcus rate-equilibrium formalism to the double-minimum potential energy surface led to the development of a model for intrinsic nucleophilicity in S 2 reactions233. The key quantities in this model are the central energy barriers, Eq, to degenerate reactions, like the one of equation 22, which are free of a thermodynamic driving force. 

PeUerite, M. J. Brauman, J. I. Intrinsic barriers in nucleophilic displacements. A general model for intrinsic nucleophilicity toward methyl centers, J. Am. Chem. Soc. 1983,105, 2672-2680. 

We recently disclosed that salts of alkali and alkaline earth metals effectively promote fhe aldol reaction of DMS enolates (Scheme 10.34) [101]. For example, fhe CaCl2-catalyzed reaction of propiophenone DMS enolate with aldehydes proceeds smoothly in DMF at 30 °C with high reaction efficiency. In the metal salt-catalyzed aldol reaction fhe counter anion of fhe metal salt plays a crucial role in rate acceleration. The activity of metal salt increases with increasing intrinsic nucleophilicity of fhe counter anion TfO metal salts work as Lewis bases to activate DMS enolates. To our surprise, the... 

Initially, the method was based on the differential reactivity conferred on each of the partners by the nature of the protecting groups and by the intrinsic nucleophilicity of the thioaryl leaving groups. However, as the method evolved, it became clear that the choice of the promoter was also an important factor to take into consideration. Indeed, it was demonstrated that a disarmed thioglycoside could be activated in the presence of powerful thiophilic promoters such as A-iodosuccinim-ide/trifluoromethanesulfonic acid (NIS/TfOH), whereas it remained inactivated in the presence of weak thiophilic reagent such as iodonium dicollidine perchlorate or methyl triflate [43,45]. 

As Bunnett has noted (4), the kinetic barrier to nucleophilic attack is affected by the thermodynamics of the reaction. If this thermodynamic contribution could be removed, then intrinsic nucleophilicities for substitution reactions could be obtained that would be independent of the leaving group. Pioneering work by Albery and Kreevoy (7), Pellerite and Brauman (8), and Lewis et al. (9) has shown that Marcus theory can be applied to methyl-transfer reactions to separate thermodynamic and kinetic contributions and provide intrinsic barriers to nucleophilic attack. One expression of Marcus theory is given in equation 1, where AE is the activation energy, AE° is the heat of reaction, and AE0 is the intrinsic activation energy or the barrier to reaction in the absence of any thermodynamic driving force. 

Although reaction 4 is exceedingly exothermic, it does not occur on every collision, and the efficiency decreases with increasing temperature (Figure 6). This finding is characteristic of a reaction where the potential surface shows two wells (i.e., two intermediates, as in reaction 3) (4). With modeling, these data may be used to derive intrinsic nucleophilicities (5) although we have yet to do this for reaction 4. 

The apparent intrinsic nucleophilicities of halide ions have been determined by the thermal decomposition of quaternary ammonium salts (19). Complica-... 

The isocyanide is intrinsically nucleophilic, whereas the a-carbon of a-isocyanoacetate becomes a nucleophile only upon deprotonation. It is therefore... 

On the other hand, trialkylhydrosilanes are capable of reducing carbonyl compounds and some activated olefins in the presence of Brc nsted or Lewis acids. Apparently, coordination of carbonyl oxygen to acid is important to activate electrophilic carbons. We thought that pentacoordinate hydridosilicates should be a good hydride transfer reagent because of the intrinsic nucleophilicity, while the significant Lewis acid character of the silicon center should activate the substrate carbonyl compounds. Reduction of carbonyl compounds with pentacoordinate hydridosilicates are expected to proceed without any additives and thus very interesting from both mechanistic and practical point of view. 

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