Localized nucleophiles

As we just argued, for reactions of electrophiles and nucleophiles/increases as the nucleophile becomes more delocalized. Thus, the series of delocalized nucleophiles, in Fig. 6.10, is more selective to changes (of any kind) that affect the gap, G, compared with the series of localized nucleophiles. This would be general for other processes as well delocalization of the single electrons in the R states of the diagram results in higher/values, and vice versa. Such trends abound in electrophile—nucleophile combinations they were analyzed also for radical addition to olefins (40), and are likely to be a general feature of reactivity. 

A third mechanism for substitution at C(sp3)-X bonds under basic conditions, elimination-addition, is occasionally seen. The stereochemical outcome of the substitution reaction shown in the figure tells us that a direct Sn2 substitution is not occurring. Two sequential Sn2 reactions would explain the retention of stereochemistry, but the problem with this explanation is that backside attack of MeO- on the extremely hindered top face of the bromide is simply not reasonable. The SrnI mechanism can also be ruled out, as the first-row, localized nucleophile MeO- and the 2° alkyl halide are unlikely substrates for such a mechanism. 

The issue of regiochemistry can be addressed by identifying sites of local electrophilicity and local nucleophilicity. This was done by calculation of a local electrophilicity index The index of nucleophilicity can be taken as / , the local Fukui function for electrophilic attack. The regiochemistry is then predicted by matching the highest local electrophilicity in the electrophilic component with the largest f for the nucleophilic component. Table 10.10 gives some values of representative dienes and dienophiles. 

Fig. 2 Reaction of a free radical with a nucleophile. (A) Localized nucleophilic radical (e.g. McjC-) and delocalized nucleophile (e.g. Me2C=NO 2) E increases with LUMO energy (SOMO constant). (B) Delocalized electrophilic radical (e.g. PhCOCHj ) with localized nucleophile E decreases as HOMO energy increases (SOMO and LUMO constant)...

They describe local electrophilicity, local nucleophilicity, and local softness, respectively. 

The nucleophilicity of 32 amine, amide, carbamate, amidine, and pyridine nucleophiles was calculated at the B3LYP/6-31G(d,p) level of theory using the gas-phase ionization potential based on the nucleophilicity index The correlation coefficient for the calculated pyridine nucleophilicity against Mayr s values was 0.947, and it was 0.987 against the inverse of the electrophilicity scale Mm. The site selectivity predicted for the nucleophiles with more than one nucleophilic centre correlates well with that predicted by the local nucleophilicity index and the philicity index m. ... 

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