Nucleophile hard/soft

In addition, a catalytic version of Tt-allylpalladium chemistry has been devel-oped[6,7]. Formation of the Tr-allylpalladium complexes by the oxidative addition of various allylic compounds to Pd(0) and subsequent reaction of the complex with soft carbon nucleophiles are the basis of catalytic allylation. After the reaction, Pd(0) is reformed, and undergoes oxidative addition to the allylic compounds again, making the reaction catalytic.-In addition to the soft carbon nucleophiles, hard carbon nucleophiles of organometallic compounds of main group metals are allylated with 7r-allylpalladium complexes. The reaction proceeds via transmetallation. These catalytic reactions are treated in this chapter. 

We can also describe the differences between these reaction types in terms of Pearson s hard-soft description (Pearson, 1966 Pearson and Songstad, 1967). Cationic micellar head groups interact best with soft bases, e.g. relatively large anions of low charge density such as bromide or arenesulfo-nate, or anionic transition states such as those for nucleophilic aromatic substitution. They interact less readily with hard bases, e.g. high charge density anions such as OH ", or anionic transition states for deacylation. 

In order to clarify the different behavior of anion 2 and 3 (Scheme 4.10) toward DMC, various anions with different soft/hard character (aliphatic and aromatic amines, alcohoxydes, phenoxides, thiolates) were compared with regard to nucleophilic substitutions on DMC, using different reaction conditions. Results were in good agreement with the hard-soft acid-base (HSAB) theory. Accordingly, the high selectivity of monomethylation of CH2 acidic compounds and primary aromatic amines with DMC can be explained by two different subsequent reactions, which are due to the double electrophilic character of DMC. The first... 

The combination of the dual electrophilic character of DMC with its reaction products allows two consecutive steps to occur in a selective way for what concerns both reaction sequence and yields first, the hard-hard reaction occurs and produces a soft anion only and second, a soft-soft nucleophilic displacement leads to the final product. Since hard-soft and soft-hard interactions are inhibited, double methylation and double carboxymethylation do not occur. 

The thermodynamic tendency of a substance to act as a Lewis base. The strength of a Lewis base depends on the nature of the acid with which the Lewis base forms a Lewis adduct. Hence, comparative measures of Lewis basicities are given by equilibrium constants for the formation of the adducts by a common reference acid. See Lewis Base Nucleophilicity Hard Bases Soft Bases Donor Number... 

Since biological systems are rich in nucleophiles (DNA, proteins, etc.) the possibility that electrophilic metabolites may become irreversibly bound to cellular macromolecules exists. Electrophiles and nucleophiles are classified as hard or soft depending on the electron density, with hard electrophiles generally having more intense charge localization than soft electrophiles in which the charge is more diffuse. Hard electrophiles tend to react preferentially with hard nucleophiles and soft electrophiles with soft nucleophiles. 

As for pyrones. the nature of the nucleophile (hard or soft) determines whether reactions occur at the carbonyl group or at the atom of the enone system. Electrophiles attack in I he benzene ring. 

Further examination of the results indicated that by invocation of Pearson s Hard-Soft Acid-Base (HSAB) theory (57), the results are consistent with experimental observation. According to Pearson s theory, which has been generalized to include nucleophiles (bases) and electrophiles (acids), interactions between hard reactants are proposed to be dependent on coulombic attraction. The combination of soft reactants, however, is thought to be due to overlap of the lowest unoccupied molecular orbital (LUMO) of the electrophile and the highest occupied molecular orbital (HOMO) of the nucleophile, the so-called frontier molecular orbitals. It was found that, compared to all other positions in the quinone methide, the alpha carbon had the greatest LUMO electron density. It appears, therefore, that the frontier molecular orbital interactions are overriding the unfavorable coulombic conditions. This interpretation also supports the preferential reaction of the sulfhydryl ion over the hydroxide ion in kraft pulping. In comparison to the hydroxide ion, the sulfhydryl is relatively soft, and in Pearson s theory, soft reactants will bond preferentially to soft reactants, while hard acids will favorably combine with hard bases. Since the alpha position is the softest in the entire molecule, as evidenced by the LUMO density, the softer sulfhydryl ion would be more likely to attack this position than the hydroxide. 

In contrast, soft electrophiles react with nucleophilic SH groups in GSH and proteins. Soft electrophiles are typically cytotoxic, such as the metabolite of paracetamol, N-acetyl-p-benzoquinoneimine (Fig. 4.73) (see also chap. 7). So reactivity with GSH depends on the hardness/softness of the electrophile. 

Environmentally relevant nucleophiles (Lewis bases) may be classified according to Pearson s HSAB principle, as hard, soft, or borderline (possessing intermediate hard/soft character) as follows (Larson and Weber, 1994) ... 

It is appropriate at this point to summarize the tendency of various nucleophiles to add to the carbonyl group. In general, the strong bases (organometallics, hydrides, negative ions) are most effective among the neutral nucleophiles, the soft ones, for example the sulfur bases, tend to be more effective in addition than the hard ones, for example the oxygen bases. 

Nucleophiles partition between the two mechanisms based on their hard-soft characteristics, with soft nucleophiles undergoing ligand attack and hard nucleophiles attacking at the metal. A limited class of nucleophiles appear capable of adding by either mechanism, with secondary factors controlling their choice of mode of addition. 

Rozhkov IN, Borisov YA (1988) Relative reactivity of F-alkenes in regard to the hard-soft nucleophiles. The fifth regular meeting of soviet-japanese fluorine chemists, Tokyo, p 75... 

To predict which of the two alkyne carbons, C1 or C2, HNC will preferentially attack, one now invokes the local hard-soft acid-base (HSAB) principle (cf. [157]), which says that interaction is favored between electrophile/nucleophile (or radical/radical) of most nearly equal softness. The HNC carbon softness of 1.215 is closer to the softness of C1 (1.102) than that of C2 (0.453) of the alkyne, so this method predicts that in the reaction scheme above the HNC attacks C1 in preference to C2, i.e. that reaction should occur mainly by the zwitterion A. This kind of analysis worked for -CH3 and -NH2 substituents on the alkyne, but not for -F. 

The properties of dimethyl carbonate, (MeO)2CO, as an ambident electrophile have been investigated by analysis of the products of its reaction with various nucleophiles having different hard-soft character. Results were in good agreement with the Hard-Soft Acid-Base theory, hard nucleophiles attacking the hard C=0 group and soft nucleophiles the soft Me group (Scheme ll).37... 

White phosphorus, a strained tricyclic system has a low nucleophilic reactivity but is highly electrophilic. 2) Attack by a nucleophile produces a reactive phosphide ion which is rapidly protonated in hydroxylic media. For high yields of a required product it is essential to trap this ion with a suitable electrophile. 3) Owing to the mutual reaction of nucleophile and electrophile the number of useful combinations is limited. In principle a combination of hard nucleophile and soft electrophile is preferred. 

Figure 3.5 Solvent shells surround hard bases rendering them less reactive nucleophiles than soft bases.

According to the concept of the hard-soft acid base, the carbon is considered more nucleophilic than the oxygen, thus more likely to react than the oxygen atom because the leaving... 

Both oxygen and nitrogen nucleophiles react more rapidly with fluoroaromatics than corresponding sulphur and carbon nucleophiles, in accordance with Hard-Soft Acid-Base principles [51]. It should be remembered, however, that the situation can become more complex with, for example, base catalysis, where the rate of the second stage becomes important under these rather unusual conditions, an order of replacement Br > Cl > F has been observed [52]. 

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