Polarizability and nucleophilicity

Abramovitch and Newman (39) found that the displacement rate ratios Mes/ Meo of0.71 fof 2 fluofopyridine and 4.7 for 2-bromopyridine agree with the HSAB principle. The F/Br mobility ratios were also deduced for the methoxide ion (28.5) and for the methanethiolate (4.3). The diminished r the bromo compound is due to attractive dispersion forces between the polarizable nucleophile and the leaving group (40). 

When the leaving group departs, its negative charge is attracted to the positive metal center, and it rapidly adds to the metal in the second step of the mechanism. The rate is enhanced by small, highly polarizable nucleophiles and soft, unsaturated... 

With soft anions crown-ethers are more efficient than quaternary salts, the reverse being observed when less polarizable nucleophiles are used. This is explained by the different extent of complexation of crown-ethers which depends not only on the complexed cation, but also on the anionic counterpart. Swelling and hydration measurements of polymer-supported crown-ethers in toluene/aqueous KY showed that the content of water in the imbibed solvent increases with the loading. This leads to a progressive polarity increase within the polymers and to a better crown-ether complexing... 

In an earlier report Bach and coworkers suggested that MesN and MesP had nearly the same gas-phase barriers with peroxyformic acid (AA 5 = 0.5 kcalmol", MP4//MP2/6-31G ) and that their relative reactivity in protic solvent is better attributed to a much greater ground-state solvation of the more basic tertiary amine than the polarizability of the phosphorus. In a more recent study, a 3.3 kcalmol" barrier difference was observed with HCO3H in favor of the P nucleophile at B3LYP/6-31- -G(d,p) (3.0 versus —0.3 kcalmol". Table 12). Thus, the less reactive f-BuO—OH is a more discriminating oxidant with a later TS and the difference in barrier heights for N versus P oxidation widens. These data also point out that rate differences should be compared for a common set of nucleophiles and that when you use oxidants of different reactivity you should... 

The increase in stability with the DMSO content is a general feature for Meisenheimer adduct formation and is observed to similar extents for pyridine as well as benzene adducts. It is mainly caused by the enhanced nucleophilicity of the RO ion, resulting from a decreased specific solvation of the charged reagent as the concentration of the protic solvent is decreased and dispersion interactions between the large, polarizable adduct and the dipolar aprotic solvent.36,83... 

In non-K-region epoxides like 86, second-order nucleophilic addition and water-catalyzed aromatization compete. Nitrogen and oxygen nucleophiles are not able to compete, whereas polarizable nucleophiles do. The factor most important is apparently the polarizability of the nucleophile rather than its basicity. The basicity of the thiolate species has little influence on the rate of reaction of 86 (Bronsted / -value = 0.2).138,139... 

Soft and polarizable nucleophiles, e.g., azide, thiol anions, and phenoxides, add readily to arene oxides, whereas harder anions like carbanions and... 

Due to the highly nucleophilic and polarizable thiocarbonyl sulfur, thioketones react with a large variety of electrophiles E+. In the case of thioaldehydes and thioketenes this... 

Only the azide anion amongst the multitude of possible nitrogen nucleophiles had reported utility in alkynyliodonium salt addition chemistry at the inception of this project. Therefore, extension of this chemistry to amines and amide derivatives occupied our attention at the outset. The requirement for a soft, polarizable nucleophile limited our options, and screening a primary amine as well as some common amide derivatives in the prototype transformation 35 + 36 - 38 led to the first sense that this goal was achievable (Scheme 6).5a c In fact, the common amine protecting group tosyl proved to be the most effective modulator of amine nucleophilicity in this assay. Interestingly, amide pKa does not... 

Solvent effects on the kinetics and mechanism of unimolecular heterolysis of commercial organohalogen compounds have been investigated.9-11 The reaction rate is satisfactorily correlated by parameters for polarity, electrophilicity, and cohesion of the solvent, whereas the solvent nucleophilicity and polarizability exert no effect. 

Bottom line sulfur nucleophiles will function as nucleophiles and not as bases. For the same reason, halides (Cl-, Br-, l-, which are all very large and very polarizable) will also function as nucleophiles and not as bases. So when you see one of these nucleophiles, you do not need to worry about elimination reactions—you will get only substitution reactions. It is very common to see the halides being used as nucleophiles, so it is very helpful to know that you do not need to worry about elimination reactions when you see a halide as the reagent. In Chapter 12, we will... 

The regioselectivity of the cleavage of cyclic sulfites depends on the nature of the nucleophile, and this dependence can be interpreted in terms of the hard and soft acid and base principle <2000T7051>. For instance, in reactions with PhONa, PhSNa, NaN3, NaCN, BnNH2, and Pr NI I2, the Sn2 attack occurs exclusively at the less sterically hindered carbon atom. In contrast, the harder, less polarizable nucleophiles BnNHNa, PhNHNa, BnONa, and BnSNa attack at both the carbon and the sulfur atoms, sometimes with a predominance at the latter <2000T7051>. 

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