Nucleophilic addition linear free energy

A quite different and complimentary approach is to assume that addition of a nucleophile to an acyl derivative (RCOX) would follow the linear free energy relationship for addition of the nucleophile to the corresponding ketone (RCOR, or aldehyde if R=H) if conjugation between X and the carbonyl could be turned off, while leaving its polar effects unchanged. This can be done if one knows or can estimate the barrier to rotation about the CO-X bond, because the transition state for this rotation is expected to be in a conformation with X rotated by 90° relative to RCO. In this conformation X is no longer conjugated, so one can treat it as a pure polar substituent. Various values determined by this approach are included in the tables in this chapter. 

Sander and Jencks introduced a linear free energy relationship for nucleophilic addition to carbonyls. The equilibrium nucleophilicity of a species HNu is given by... 

TABLE 1.5 Linear free energy relationships for addition to carbonyl groups variation in nucleophile. ... 

The equilibria of addition of the nucleophiles HjO, HSO3, NH2OH, NH2CONH2, HSCH2CH2OH, and H2S to quinazoline were examined, and a linear free-energy relationship was noted between log and the y values of the nucleophile. The latter values are parameters that give a measure of the ability of the nucleophile to add to aldehydes or ketones. 

The nucleophilicities are found to be dependent on electronic, steric, and symbiotic effects, and limited series obeyed a constant selectivity , a reactivity-selectivity or a dual-parameter linear free-energy relationship. The conclusion made was that because of different blends of the effects, the construction of a substrate-independent nucleophilicity scale was impossible at present, but an approximate scale was presented. In nucleophilic reactions on relatively long lived vinyl cations, the steric effects predominate, but at constant steric effects, reactivity-selectivity relationships were found for very short series of substrates. Additional data are required for constructing more reliable nucleophilicity scales toward neutral and positively charged vinylic carbons. 

By about 1980, a reasonable empirical understanding of carbenic philicity seemed to be at hand electrophiles, ambiphiles, and nucleophiles had been identified and could be assigned m xy or p xv values that reflected the magnitude and character of their selectivity during their additions to alkenes. And yet, our rationalization of these reactions only in terms of relative reactivities and linear free energy relations was surely incomplete. 

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