Substrates reactivity toward nucleophilic substitution

Within the past several years, we have examined the synthesis and reactions of several classes of polymers related to PECH. We have adopted three simple approaches to the preparation of polymeric substrates more reactive than PECH toward nucleophilic substitution. We have i). removed the 8-branch point by extension of the side chain, ii). replaced the chloride leaving group by a more reactive bromide and iii). replaced the backbone oxygen atom by a sulfur atom that offers substantial anchimeric assistance to nucleophilic... 

Substituted bicycloalkyl halides are very unreactive toward nucleophilic substitution reactions. The low reactivity in S l reactions has been attributed to the fact that a planar configuration at the bridgehead carbon cannot be obtained without the introduction of considerable strain119. On the other hand, the S 2 reaction is precluded because a backside approach of the nucleophile cannot occur at a bridgehead position for a steric reason. The lack of reactivity of 1 -halobicycloalkanes toward nucleophiles by polar mechanisms makes them attractive substrates for the S l mechanism. 

Allyl derivatives 11 with identical substituents at Cl and C3 are an important class of substrates for enantioselective allylic substitution (Scheme 10). Starting from either enantiomer (11 or ent-ll) the same allyl-palladium complex 12 is formed. Therefore, the first part of the catalytic cycle leading to this intermediate usually is irrelevant for the stereoselectivity of the overall reaction [31]. The two termini of the free allyl system are enantiotopic. If the catalyst is chiral, they become diasterotopic in the allyl-metal complex and, therefore, may exhibit different reactivities toward nucleophiles. Under the influence of a suitable chiral ligand attached to palladium, nucleophilic attack can be rendered regioselective leading preferentially either to product 13 or its enantiomer ent-l3. 

The substitutions with nucleophilic radicals become particularly interesting only with electron-deficient aromatic substrates, as the ionic nucleophilic substitutions. Carbon free radicals are the most common nucleophilic radicals and they are obviously among the most important organic free radicals. Heteroaromatic bases on the other hand are electron-deficient aromatic substrates which readily react with nucleophilic species. The protonation of heteroaromatic bases strongly increases their electron-deficient nature and therefore the reactivity towards nucleophilic reagents, while the reactivity towards electrophilic species is strongly... 

Nucleophilic substitution of common nucleofuges such as halogenes is one of the most well-studied reactions in the chain-fluorinated diazine series. Analysis of the literature data shows that nearly 90 % examples of chain-fluorinated halodiazine reactions with N-, S-, and 0-nucleophiles refer to pyrimidine derivatives (Table 47). Only 2- and 4-fluoroalkyl-5-halopyrimidines have received almost no attention in these transformations. Data on nucleophilic substitution of halogens in chain-fluorinated diazines correlates with the accessibility of the corresponding substrates, and to a lesser extent - with their reactivity towards nucleophiles. 

Methanesulfonates. The most common use of methanesulfonyl chloride is for the synthesis of sulfonate esters from alcohols. This can be readily accomplished by treatment of an alcohol with mesyl chloride in the presence of a base (usually Triethy-lamine or Pyridine). The methanesulfonates formed are functional equivalents of halides. As such they are frequently employed as intermediates for reactions such as displacements, eliminations, reductions, and rearrangements. Selective mesylation of a vicinal diol is a common method of preparation of epoxides." Alkynyl mesylates can be used for the synthesis of trimethylsilyl allenes. Oxime mesylates undergo a Beckmann rearrangement upon treatment with a Lewis acid. Aromatic mesylates have been used as substrates for nucleophilic aromatic substitution. Mesylates are more reactive than tosylates toward nucleophilic substitution, but less reactive toward solvolysis. 

It is more difficult to interpret micellar effects upon reactions of azide ion. The behavior is normal , in the sense that k /kw 1, for deacylation, an Sn2 reaction, and addition to a carbocation (Table 4) (Cuenca, 1985). But the micellar reaction is much faster for nucleophilic aromatic substitution. Values of k /kw depend upon the substrate and are slightly larger when both N 3 and an inert counterion are present, but the trends are the same. We have no explanation for these results, although there seems to be a relation between the anomalous behavior of the azide ion in micellar reactions of aromatic substrates and its nucleophilicity in water and similar polar, hydroxylic solvents. Azide is a very powerful nucleophile towards carboca-tions, based on Ritchie s N+ scale, but in water it is much less reactive towards 2,4-dinitrohalobenzenes than predicted, whereas the reactivity of other nucleophiles fits the N+ scale (Ritchie and Sawada, 1977). Therefore the large values of k /kw may reflect the fact that azide ion is unusually unreactive in aromatic nucleophilic substitution in water, rather than that it is abnormally reactive in micelles. 

Rogne (1970) has measured the reactivity of some of the same nucleophiles toward benzenesulfonyl chloride in water at 25°. When log km for reaction of these nucleophiles with PhSOjCl is plotted vs. the log values for the same nucleophiles from Table 10, one obtains a good straight line relationship with a slope of about 0.8. This shows that the reactivity pattern observed with PhSOjSOjPh and shown in Table 10 is representative of what will be observed generally in nucleophilic substitution at the sulfonyl sulfur of reactive sulfonyl substrates. 

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