And nucleophilic addition

The initial discussion in this chapter will focus on addition reactions. The discussion is restricted to reactions that involve polar or ionic mechanisms. There are other important classes of addition reactions which are discussed elsewhere these include concerted addition reactions proceeding through nonpolar transition states (Chapter 11), radical additions (Chapter 12), photochemical additions (Chapter 13), and nucleophilic addition to electrophilic alkenes (Part B, Chi iter 1, Section 1.10). 

Fig. 8.3. Three-dimensional potential energy diagram for addition of a proton and nucleophile to a caibonyl group, (a) Proton transfer complete before nucleophilic addition begins (b) nucleophilic addition complete before proton transfer begins (c) concerted proton transfer and nucleophilic addition.

ATP is activated by coordination to magnesium ion, and nucleophilic addition of a fatty acid caiboxylate to phosphorus then yields a pentacoordinate intermediate. . ... 

Acid-catalyzed ester hydrolysis can occur by more than one mechanism, depending on the structure of the ester. The usual pathway, however, is just the reverse of a Fischer esterification reaction (Section 21.3). The ester is first activated toward nucleophilic attack by protonation of the carboxyl oxygen atom, and nucleophilic addition of water then occurs. Transfer of a proton and elimination of alcohol yields the carboxylic acid (Figure 21.8). Because this hydrolysis reaction is the reverse of a Fischer esterification reaction, Figure 21.8 is the reverse of Figure 21.4. 

Carbonyl condensation reaction (Section 23.1) A reaction that joins two carbonyl compounds together by a combination of a-substitution and nucleophilic addition reactions. 

The magnitude of the electrical effect is somewhat less in the case of radical addition than it was in the case of electrophilic and nucleophilic addition. 

The possible reaction pathways for the stereoselective E- and Z-allylation are illustrated in Scheme 7. 1-Silyl-l,3-dienes 22 react with a Ni-H species in the presence of PPI13 to provide a syn-it-allylnickel species 24, the least substituted allylnickel species, which undergoes nucleophilic addition to an aldehyde at the least substituted allylic terminus to provide ( )-allylsilanc ( )-23. It should be noted that the regioselectivities observed for the Ni-H addition to a diene 22 and nucleophilic addition of 24 to aldehydes are opposite to those observed so far in many precedents in this review (e.g., Eqs. 4 and 6). 

The effect of metal basicity on the mode of reactivity of the metal-carbon bond in carbene complexes toward electrophilic and nucleophilic reagents was emphasized in Section II above. Reactivity studies of alkylidene ligands in d8 and d6 Ru, Os, and Ir complexes reinforce the notion that electrophilic additions to electron-rich compounds and nucleophilic additions to electron-deficient compounds are the expected patterns. Notable exceptions include addition of CO and CNR to the osmium methylene complex 47. These latter reactions can be interpreted in terms of non-innocent participation of the nitrosyl ligand. 

Thus methyl and chalcoformaldehyde complexes of osmium are accessible by both electrophilic addition to a neutral d8 methylene complex and nucleophilic addition to a cationic d6 methylene complex. 

These reactions comprise nucleophilic SN2 substitutions, -eliminations, and nucleophilic additions to carbonyl compounds or activated double bonds, etc. They involve the reactivity of anionic species Nu associated with counterions M+ to form ion-pairs with several possible structures [52] (Scheme 3.4). 

To what extent is the partitioning of simple aliphatic and benzylic a-CH-substituted carbocations in nucleophilic solvents controlled by the relative thermodynamic driving force for proton transfer and nucleophile addition reactions It is known that the partitioning of simple aliphatic carbocations favors the formation of nucleophile adducts (ksjkp > 1, Scheme 2) and there is good evidence that this reflects, at least in part, the larger thermodynamic driving force for the nucleophilic addition compared with the proton transfer reaction of solvent (A dd U Scheme 6).12 21,22,24... 

Table 2 gives rate and equilibrium constants for the deprotonation of and nucleophilic addition of water to X-[6+]. These data are plotted as logarithmic rate-equilibrium correlations in Fig. 5, which shows (a) correlations of log ftp for deprotonation of X-[6+] and log Hoh for addition of water to X-[6+] with logXaik and log KR, respectively (b) correlations of log(/cH)soiv for specific-acid-catalyzed cleavage of X-[6]-OH (the microscopic reverse of nucleophilic addition of water to X-[6+]) and log( H)aik for protonation of X-[7] (the microscopic reverse of deprotonation of X-[6+]) with log Xafc and log XR, respectively. 

A comparison of rate and equilibrium constants for partitioning of the cyclic carbocation [18+] with those for the l-(4-methylphenyl)ethyl carbocation Me-[6+] (Table 5) shows that placement of the cationic benzylic carbon in a five-membered ring results in the following complex changes in the reactivity of the carbocation towards deprotonation and nucleophilic addition of solvent (Scheme 15). 

The results of studies of the acid-catalyzed hydration of oxygen-, sulfur-, seleno-and nitrogen-substituted alkenes and the relevance of this work to partitioning of the corresponding carbocation intermediates (Chart 1) between deprotonation and nucleophile addition was reviewed in 1986.70. We present here a brief summary of this earlier review, along with additional discussion of recent literature. 

The value of kjkp = 17000 for partitioning of the acetophenone oxocarbenium ion [12+] between deprotonation and nucleophilic addition of water1516... 

The partitioning of ferrocenyl-stabilized carbocations [30] between nucleophile addition and deprotonation (Scheme 18) has been studied by Bunton and coworkers. In some cases the rate constants for deprotonation and nucleophile addition are comparable, but in others they favor formation of the nucleophile adduct. However, the alkene product of deprotonation of [30] is always the thermodynamically favored product.120. In other words, the addition of water to [30] gives an alcohol that is thermodynamically less stable than the alkene that forms by deprotonation of [30], but the reaction passes over an activation barrier whose height is equal to, or smaller than, the barrier for deprotonation of [30], These data require that the intrinsic barrier for thermoneutral addition of water to [30] (As) be smaller than the intrinsic barrier for deprotonation of [30] (Ap). It is not known whether the magnitude of (Ap — As) for the reactions of [30] is similar to the values of (Ap - As) = 4-6 kcal mol 1 reported here for the partitioning of a-methyl benzyl carbocations. 

The partitioning of simple tertiary carbocations, ring-substituted 1-phenylethyl carbocations, and cumyl carbocations between deprotonation and nucleophilic addition of solvent strongly favors formation of the solvent adduct. The more favorable partitioning of these carbocations to form the solvent adduct is due, in part, to the greater thermodynamic stability of the solvent... 

The incorporation of a cationic benzylic carbon into a five-membered ring results in complex changes in the reactivity of the carbocation toward deprotonation and nucleophilic addition of solvent (Scheme 15). 

This section focuses on the preparation of fluorinated compounds through asymmetric hydrogenation/reduction reactions and nucleophilic additions by listing some examples. The first successful example of catalytic asymmetric hydrogenation of a fluoro-compound was reported by Konig et al.81... 

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