Nucleophilicity hard and soft

Fig. 23. Reactions of bromoarenes with hard (and soft) nucleophiles catalyzed by nickel, copper and palladium...

S, I) are more polarizable (they are further away from the nucleus), and since larger soft species have, in general, lower solvation energies, they are better nucleophiles as compared to smaller hard species. (For definition of the term hard and soft nucleophiles, see Box 13.1.) Thus, we can qualitatively understand why, for example, nucleophilicity increases from F to Cl to Br to V (Table 13.3), and why HS- is a stronger nucleophile than OH". 

Nucleophilic reactions with water 77 Reactions with water as a base 87 Reactions of nucleophiles other than water 90 Reactivity, selectivity, and transition state structure 105 Hard and soft nucleophiles 110 Summary and conclusions 112 Acknowledgments 114 References 114... 

It is not intended to pursue this discussion to a firmer conclusion. However, it is reasonable to infer that our understanding of reactivity and selectivity in carbocations has been brought to a point where the origins of differences in reactivities of hard and soft nucleophiles and of lack of correlation of rate and equilibrium constants have been greatly clarified. Particularly, in the hands of... 

Richard, the Marcus analysis, allied to the concept imbalance of bond making and charge development at the transition state, has provided an effective framework for tackling one of the outstanding problems for a general interpretation of reactivity. A reasonable conclusion might be that further measurements of equilibrium constants will be required to support and test the level of understanding achieved so far, and to probe more deeply the interpretation of hard and soft nucleophilicity in its application to reactions of electrophilic carbon atoms. 

A particular difficulty arises for the comparison of hard and soft nucleophiles. This difficulty indeed is amplified if one goes beyond carbocation reactions to consider softer or harder electrophilic centers, such as transition metals or protons. Interpreting differences between reacting atoms presents an ultimate challenge for attempts to understand reactivity. Richard has gone a considerable way toward offering a rational analysis of the principal factors to be considered in such an endeavor. However, this is one issue likely to attract attention in the next one hundred years of carbocation chemistry and in the wider field of electrophile nucleophile combination reactions. 

The energy of the HOMO (EHomo) is directly related to the ionization potential and characterizes the susceptibility of the molecule to attack by electrophiles. On the other hand, EHOMO is directly related to the electron affinity and characterizes the susceptibility of the molecule toward attack by nucleophiles. Both the E, IOMO and LUMO energies are important in radical reactions. The concept of hard and soft nucleophiles and electrophiles has... 

The methodology suffers from competition between syn- and anti-mechanisms in acyclic cases. Indeed, the pathway may depend on the nature of nucleophile and substrate.78139 In addition, there is no clearcut differentiation between hard and soft nucleophiles in the model described. 

OCH3 and NH3, give exclusive attack at the hard electrophilic centres, i.e. C—F, whereas soft nucleophiles displace bromine. This is further evidence for the importance of ion-dipole interactions, regarding attack at C—F bonds. Reactions of perfluoro-quinoline and -isoquinoline with hard and soft nucleophiles have also revealed a sensitivity towards a change in orientation of attack with the nature of the nucleophile [114] (Figure 9.42). 

Hard and soft nucleophiles in substitution reactions are discussed in Chapter 17. 

Systematic exploitation of the different susceptibilities of the different positions of perfluoroaromatic compounds can be used as a tool for combinatorial synthesis of (fluoro)aromatic compounds. The feasibility of this concept was recently demonstrated by R. D. Chambers and coworkers who used the pentafluoropyridine system as an example [99] (Scheme 2.43). Further differentiation of the reactivity toward hard and soft nucleophiles was achieved by partial replacement of fluorine by bromine in this system. 

K Fuji, K Ichikawa, M Node, E Fujita. Hard and soft nucleophile system New efficient method for removal of benzyl protecting groups. J Org Chem 44 1661-1664, 1979. 

Using the concept of hard and soft nucleophiles/electrophiles, it is possible to classify the reactivity broadly in terms of either charge or Frontier Molecular Orbital (FMO) controlled attack respectively guided by Eq. 1 [12]. 

Allylic alkylations. Highly regioselective alkylation of both hard and soft nucleophiles (phenolates, sulfonamides, and phenylsulfonylacetic esters, respectively) is also possible with the Rh catalyst modified by the added (MeOl P, The countercation seems to play an important role in the displacement with alkali phenolates to afford branched allylic ethers thus, reaction with Li salts shows the highest regioselectivity but the product yields are low. The best compromise is to use Na phenolates. 

Table 2 Examples of hard and soft electrophiles and hard and soft nucleophiles...

In the reaction of the bromoacyl chloride with methanol, attack occurs at the carbonyl group with an alcohol because oxygen nucleophiles are hard nucleophiles (controlled by charge interactions). If we want to displace the a-bromo group we can use any soft (orbital-dominated) nucleophile. Triphenylphosphine (PhjP) is particularly important—the product is a phosphonium salt, employed in Wittig reactions and discussed in Chapters 11 and 27. Hard and soft nucleophiles in substitution reactions are discussed in Chapter 15. 

The practicability of synthesis TM 4.5 according to the disconnection that includes poor simplification is confirmed by the next example, which also serves as an introduction to the important concept of hard and soft nucleophiles and electrophiles. 

The concept of hard and soft acids and bases (HSAB) is usually related to the physico-chemical properties of organic compounds and is not much recognized in synthetic organic chemistiy [15, 16]. There is also the less often used concept of hard and soft nucleophiles and electrophiles [17]. The fundamental distinction between these two concepts, i.e., between basicity and nucleophiUcity on the one hand and acidity and electrophilicity on the other, lies in that fact that basicity and acidity are thermodynamic properties, whereas nucleophiUcity and electrophUicity are kinetic terms. 

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