Nucleophilic selectivity

In contrast, considering the characteristics of the substituent groups currently used in the chlorine replacements of polydichlorophosphazene, it can be immediately realized that they can be very variable depending on the chemical structure of the nucleophile selected for these reactions. A list of the preferred chemical compounds usually exploited for the phosphazene substitutional processes is reported in Table 4. 

In the reactions mentioned in the preceding sections, several "stereoselective processes have been involved. Various examples have verified that the extension of singly-occupied MO determines the favorable spatial direction of interaction with other species. If there are two such nonequivalent directions in the molecule, the reaction will become stereoselective. Two or more hydrogen atoms attached to the same carbon atom are in some cases nonequivalent. Such a nonequivalence becomes a cause of stereoselectivity and has been explained theoretically. Also several cases have been mentioned in which some nucleophiles selectively attack the molecule from a certain spatial direction. 

Scheme 11.2 illustrates the conventional sequence for the manufacture of DAST brighteners. However, it is not always necessary and may not be desirable for DAS to be the nucleophile selected for the first step. In principle the three nucleophiles can be reacted in any order, but it is preferable for the most nucleophilic amine to react last in order to avoid forcing conditions during removal of the last remaining chloro substituents. Alkylamines react more readily than alcohols, thus ensuring that alkanolamines yield their hydroxyalkylaminotriazine derivatives. 

From their high reactivity and nucleophilic selectivity, it seems likely that N-acetoxy arylamines readily undergo heterolytic... 

When 3-(4-chlorofurazanyl-3-Ar(0)AT-azoxy)-4-nitrofurazan 218 reacts with weak bases and nucleophiles, selective attack on the carbon atom bonded to the nitro group occurs, but no products formed by substitution of the chlorine was observed (Equation 43) <2003CHE1357>. 

This reaction has been extensively used for the synthesis of polyfunctionalized piperidines with a wide range of nucleophiles selected and representative examples are collected in Table 15. From these results, hydrides, Grignard reagents, aluminium derivatives, allylsilane, as well as aromatics can be used as nucleophiles to give the corresponding C-8a functionalized compounds in good yields and, in most cases, excellent selectivities. 

The descending nucleophile selectivity (A az/A s)obsd on the left-hand limb of... 

Specific acid-catalysed solvolysis of l-methoxy-l,4-dihydronaphthalene or 2-methoxy-l,2-dihydronaphthalene in 25% acetonitrile in water has been found to yield mainly the elimination product, naphthalene, along with a small amount of 2-hydroxy-1,2-dihydronaphthalene, there being no trace of either the 1-hydroxy-1,4-dihydronaphthalene or the rearranged ether. The nucleophilic selectivity, ns/ hoh = 2.1 X 10", between added azide ion and solvent water has been estimated for the relatively stable = 1 x 10 s ) intermediate benzallylic carbocation for which the barrier to dehydronation is unusually low k = 1.6 x 10 ° s ), as evidenced by the large elimination-to-substitution ratio with solvent water as base/nucleophile. The kinetics of acid-catalysed solvolysis of 1-hydroxy-1,4-dihydronaphthalene and 2-hydroxy-1,2-dihydronaphthalene have also been studied. 

The point of the change from a stepwise to a concerted mechanism for nucleophilic substitution at X-l-Cl may be detected as an upward break in the observed nucleophile selectivity nu/ s with decreasing stability of the putative intermediate X-1 (Fig. 2.2). Figure 2.5 shows that the position of this break and the change in mechanism shifts to more electron-withdrawing X as the reactivity of the nucleophile is decreased, from X = 4-F for... 

Figure 2.5. Nucleophile selectivities determined from product analysis for the reactions of ring-suhstituted 1-phenylethyl derivatives (X-l-Y) with azide ion, acetate ion and methanol in 50 50 (v/v) water/trifluoroethanol. The selectivities are plotted against the appropriate Hammett substituent constant or a. Leaving group Y ( ) ring-suhstituted benzoates ( ) chloride (T) dimethyl sulfide (A) tosylate.

From the relative reactivities in Table 7.3, we conclude that 7a is dominant for CH3CCI and CCI2, which exhibit electrophilic selectivity toward the alkenes. On the other hand, CH3OCCH3 displays strongly nucleophilic selectivity toward the electron-poor alkenes. Resonance donation from the methoxy oxygen atom to the carbene Ip orbital (8, Fig. 7.7) is sufficiently strong to render CH3OCCH3 a nucleophilic carbene for which a 71 carbene to alkene electron donation is dominant in the transition state (viz., 7b). 

Finally, addition reactions of the isolable phosphasilylcarbenes (13) to such electron-poor substrates as methyl acrylate, C4F9CH=CH2, and styrene afford cyclopropanes. The additions of 13a to (E)- or (Z)-p-deuteriostyrene are stereospecific, and the competitive additions of 13b to ring-substituted styrenes exhibit nucleophilic selectivity, consistent with singlet, nucleophilic carbene addition (Fig. 7.8). ... 

Oxocarboxylic acid esters (78JA4225 85TH1) offer two distinct electrophilic sites to amine (II), the nucleophile. Selective nucleophilic attack at the ester function of (I) may be accomplished by selecting the reaction temperature. 

Vogel, E.W. (1989) Nucleophilic selectivity of carcinogens as a determinant of enhanced mutational response in excision repair-defective strains in Drosophila-, effects of 30 carcinogens. Carcinogenesis, 10, 2093-2106... 

Solvolysis of the R,R and R,S isomers of 2-bromo-9-(l-X-ethyl)fluorenes, X = Cl, Br, I, or OBs, in 25% (v/v) acetonitrile in water has been studied with respect to rates of formation of elimination products and of substitution products (X = OH or NHCOMe).142 The parent 9-(l-X-ethyl)fluorenes and the 2,2/-dibromo-9-(l-X-ethyl)-fluorenes were also studied. Various effects of leaving group and of the presence of nucleophiles on the competition between the reactions were observed and the Bronsted equation was applied to the results for the elimination reactions. A related study of solvolysis of 9-(X-methyl)fluorenes, X = I, Br, or Bs, was also carried out, in which the Swain-Scott equation was applied to nucleophilic selectivities in the S 2 reactions.143... 

Far from confirming a dependence of nucleophilic selectivity on the reactivity of the carbocations, Ritchie observed that selectivities were unchanged over a 106-fold change in reactivity.15 He enshrined this result in an equation (29) analogous to that of Swain and Scott, but with the nucleophilic parameter n modified to N+ to indicate its reference (initially) to reactions of cations, and with the selectivity parameter s taken as 1.0, that is, with no dependence of the selectivity of the cation on its reactivity (as measured by the rate constant for the reference nucleophile, kn2o for water). 

Carbon-sulphur double bonds also undergo nucleophilic attack in a similar fashion to carbon-oxygen double bonds except in the cases of thiophilic addition, where the nucleophile selectively attacks the sulphur56 (Scheme 9). 

Additions to styrenes in aqueous or alcoholic solutions in the presence of external nucleophiles (e.g. PhSH, EtSH, AcO- and others) have been investigated. Enhanced nucleophilic selectivity, fc(Nu) A(h20) has been observed for photoadditions61. 

The descending nucleophile selectivity (7left-hand limb of Fig. 1 for stepwise solvolysis of R-X is due to the increase in ks (s-1), with decreasing stability of the carbocation intermediate, relative to the constant value of /taz (M-1 s-1) for the diffusion-limited addition of azide anion. The lifetime for the carbocation intermediate R+ eventually becomes so short that essentially no azide ion adduct forms by diffusion-controlled trapping, because addition of solvent to R+ occurs faster than escape of the carbocation from the solvent cage followed by addition of azide ion (k s > k-d). Now, the nucleophile adduct must form through a preassociation mechanism, where the azide anion comes together in an association... 

Fig. 1 A hypothetical plot of azide ion selectivity fcaz/fcs (M-1) against the reactivity of the carbocation intermediate of solvolysis of R-X in aqueous solution (Scheme 4). The descending limb on the left hand side of this plot is for reactions where the value of ks (s-1) is increasing relative to the constant value of k (M-1 s-1) for diffusion-limited addition of azide ion to the carbocation. The constant nucleophile selectivity is for reaction of R-X by a preassociation mechanism.

Doubly (and even triply) charged anions appeared on the horizon of organic chemistry relatively recently, They were immediately recognized as extremely useful intermediates due to the synthetic opportunities offered by their unique pattern of reactivity. Besides the dianion 174, the dianions of carboxylic acids 178 (Scheme 2.82), propargylic dianion 179, and the dianion 180 derived from propargyl alcohol are now widely used as nucleophiles. Selectivity in electrophilic attack for these species is governed in much the same way as was described for 174 the least-stabilized anionic center is the preferential site of attack by the electrophile (marked with an asterisk in Scheme 2.82). 

In both cases, the nucleophile selects the less substituted allylic site and ignores an equali-. substituted site that is not aUylic. Notice that the more highly substituted alkene is formed in bo ... 

Query, C.C., Moore, M.J. and Sharp, P.A. (1994). Branch nucleophile selection in pre-mRNA splicing evidence for the bulged duplex model. Genes Dev. 8, 587-597 (1994). 

In a nice exemplification of the mesomeric interaction between indole nitrogen and a 3-carbonyl, which renders the 3-carbonyl somewhat amide-like (see also 20.11), 2,3-dicarboxylic acid anhydrides react with some nucleophiles selectively at the 2-carbonyl inductive withdrawal by the ring nitrogen may also play a part in achieving this selectivity. ... 

What about a nucleophilic carbene, for which negative charge should build up on the olefinic carbon atoms during the carbene addition cf. 5 With ArCH=CH2 substrates, electron-withdrawing aryl substituents would stabilize such a transition state and the p value should be positive. There are several examples of this phenomenon. For example, cycloheptatrienylidene, 10, adds to / -substituted styrenes with p = -t-1.02 - 1.05 (vs. a) consistent with a nucleophilic selectivity that seems to implicate the aromatic resonance form 10a as an important feature of the carbene. [45] It is satisfying to compare this result with p = -0.76 (vs. a) or -0.46 (vs. a" ") for additions to styrenes of cyclopentadienylidene, 11, where contributions of the cyclopentadienide form (11a) would render the carbene electrophilic. [46] However, these conclusions are too facile. There is reason to believe that the chemistry attributed to 10 might in fact be due to its allenic isomer 12. [47] And the electronic structure of 11 is also more complicated than the simple depiction above. [48]... 

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