Nucleophilic participation

Although nucleophilic participation at the transition state is slight it is enough to ensure that substitution proceeds with inversion of configuration... 

The importance of solvent participation in the borderline mechanisms should be noted. Nucleophilic participation is minimized by high electronegativity, which reduces the Lewis basicity and polarizability of the solvent molecules. Trifluoroacetic acid and perfiuoro alcohols are among the least nucleophilic of the solvents used in solvolysis studies. These solvents are used to define the characteristics of reactions proceeding without nucleophilic solvent participation. Solvent nucleophilicity increases with the electron-donating capacity of the molecule. The order trifluoroacetic acid < trifluoroetha-nol <acetic acid < water < ethanol gives a qualitative indication of the trend in solvent nucleophilicity. More will be said about solvent nucleophilicity in Section 5.5. 

The 2-adamantyl system has been used as a model reactant for defining the characteristics of ionization without nucleophilic participation. The degree of nucleophilic participation in other reactions can then be estimated by comparison with the 2-adamantyl system. ... 

The occurrence of nucleophilic participation is also indicated by a rate enhancement relative to the rate of solvolysis of n-butyl p-bromobenzenesulfonate. The solvolysis rates of a series of cu-mefhoxyall l p-bromobenzenesulfontes have been determined. A maximum rate is again observed where participation of a methoxy group via a live-membered ring is possible (see Table 5.20). 

Nucleophilic participation is important only for esters of alcohols that have pK <13. Specifically, phenyl and trifluoroethyl esters show nucleophilic catalysis, but methyl and 2-chloroethyl esters do not. This result reflects the fete of the tetrahedral intermediate that results fi om nucleophilic participation. For relatively acidic alcohols, the alkoxide group can be eliminated, leading to hydrolysis via nucleophilic catalysis ... 

A variety of aryl systems have been explored as substrates in the Knorr quinoline synthesis. Most notable examples are included in the work of Knorr himself who has demonstrated the high compatibility of substituted anilines as nucleophilic participants in that reaction. In the case of heteroaromatic substrates however, the ease of cyclization is dependent on the nature and relative position of the substituents on the aromatic ring." For example, 3-aminopyridines do not participate in ring closure after forming the anilide... 

Evidence that the actual methylation of the anion can be divided into SnI, Eq. (3), and Sx2 types, Eq, (4), is provided by a whole series of investigations. " The terms S l and 8 2 must be taken to mean reactions with, respectively less or greater nucleophilic participation of the anion in the transition state. The importance of oriented ion pairs" in the solvents of low polarity frequently used in reactions involving diazomethanc, e.g., the ions formed by a diazoalkane and benzoic acid in ether, should be emphasized. The expression oriented ion pair means that, because of insufficient solvation, the ions are not individually solvated but exist as ion pairs within a solvent cage. The orientation within the ion pair is defined electrostatically, and this orientation fixes the path for the productdetermining step. Several indications (cf, foo otes 22-24) in the literature indicate the occurrence of carbonium ions and oriented ion pairs in Broensted-type equilibria of the type of Eq. (2). 

The kinetics of cleavage of some of these compounds have been measured by dilatometry and in other acidic media, and the rate coefficients and relative rates are given in Table 233658, 673, 686, 687. It can be seen that there is relatively little variation in the spread of rate coefficients with change in the acid and this argues against nucleophilic participation of the acid in the rate-determining step... 

With acetoxy derivatives, the 2,3-syn isomer is preferred as a result of direct nucleophilic participation by the carbonyl oxygen. 

The nucleophiles participating in reaction with QM3 are typically obvious from the QM linkage identified in the products of all deoxynucleosides except for dA. Direct reaction to form the observed adduct at the exo 6-amino group of dA was still considered surprising due to its weak nucleophilicity, and an alternate pathway involving initial reaction at the most nucleophilic dA N1 followed by a Dimroth rearrangement that interconverts the N1 to the 6-amino groups seemed more reasonable... 

Alternatively, the transmetalation can be facilitated by increasing the nucleophilicity of the carbon nucleophile participating in the cross-coupling, which is most often done by increasing the electron density on the metal by coordination of extra anionic ligands. Two distinct approaches to nucleophilic activation are (i) the addition of appropriate Lewis bases to the reaction mixture (nucleophilic catalysis) or (ii) the use of a preformed, electron-rich, organo-metallic reagent with enhanced nucleophilicity. 

Nucleophilic participation by the neighbouring acetamido-group in the substrate has also been postulated, but substrates lacking this group have been developed which give enzymatic rates (Raftery and Rand-Meir, 1968). It is therefore not necessary to invoke such participation to explain the rates attained with the enzyme. 

When the hydroxyl group is acetylated, the svn isomer is preferred. This result is attributed to direct nucleophilic participation by the carbonyl oxygen of the ester. 

The aqueous methanolysis of 3,4-dihydro-27f-pyrano[3,2-(r]pyridinium a-D-A -acetylneuraminoate has been studied and is believed to proceed via dissociative transition states with no intramolecular nucleophilic participation by the anomeric carboxylate group <2004JP0478>. The synthesis of the starting substituted sugar is also reported. 

Figure 5.6 Distinct mechanisms, (a) Sw2. (b) Ionization to an ion pair with nucleophilic participation by solvent, (c) Limiting Swl.

Diallylpalladium complexes derived from the dimerization of butadienes have been isolated and found to contain both an V and an V-allyl unit- Although it is difficult to discern which allyl moiety is reacting, treatment of this complex with acetylenedicaiboxylate or DO Ac yields products consistent with nucleophilic participation by the V-fragment (equations 119 and 120).318-319... 

The application of correlation analysis of solvent effects to mechanistic studies of solvolysis has been reviewed by Takeuchi in Japanese.110 The article mainly covers die behaviour of tertiary chloro compounds. Tins author s research group has continued experimental studies in this area.111-113 Rates of solvolysis of 2-chloro-2,4-trimethylpentane have been measured in 17 solvents and analysed through the extended Grunwald-Winstein equation, which includes a term for nucleophilic participation.111... 

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