Mechanisms nucleophilic alkyl substitution

The reaction between an alkoxide ion and an aryl halide can be used to prepare alkyl aryl ethers only when the aryl halide is one that reacts rapidly by the addition-elim mation mechanism of nucleophilic aromatic substitution (Section 23 6)... 

Rossi, R. A. Pierini, A. B. Palacios, S. M. Nucleophilic substitution by the SrnI mechanism on alkyl halides. Adv. Free Radical Chem. 1990, 3, 193-252. 

The amine product plays a critical role, as it deprotonates the H2 complex 18 to regenerate the catalytically active 17. This also prevents side reactions based on nucleophilic ring opening of the aziridinium cations by the amine products. Alkyl substituted aziridinium cations react via a classical SN2-mechanism. 

Nucleophilic substitution reactions on unactivated alkyl halides have been known for a long time. The available mechanisms depend on the aliphatic moiety, the nucleophile, the leaving group and the reaction conditions118. Besides the polar mechanisms of nucleophilic substitution reactions (S l, S 2 and related mechanisms), several alkyl halides react with nucleophiles by an ET reaction. 

These observations are easily explained by another simple reaction mechanism, nucleophilic substitution of an alkoxide on silicon (12). In this case, the basic alkoxide oxygens tend to repel the nucleophile, OH, and the bulkier alkyl groups tend to crowd it. Therefore, more highly hydrolyzed silicons are more prone to attack. Because this mechanism would have a pentacoordinated silicon atom in the activated complex, hydrolysis of a polymer would be more sterically hindered than hydrolysis of a monomer. Reesterification would be much more difficult in alkaline solution than in acidic solution, because silanols are more acidic than the hydroxyl protons of alcohols and would be deprotonated and negatively charged at a pH lower than the point at which the nucleophile concentration becomes significant (ii). Thus, although hydrolysis in alkaline solution is slow, it still tends to be complete and irreversible, if extensive polymerization does not occur first. 

Tertiary alcohols such as V do not undergo this reaction according to some experimental evidence. Any increase in the alkyl substitution at the carbinol carbon, however, would be expected to facilitate both S l and Sn2 processes. Evidently, the basis of the nucleophilic displacement mechanism is not as solid as we originally thought. 

Tetraalkylborates are mild and selective alkylation reagents [186, 187], and they are commonly considered as sources of nucleophilic alkyl groups (R ) just as borohy-drides are depicted as hydride (H ) sources. However, since organoborates represent excellent electron donors (see Table 5, Section 2.2.1), the question arises as to what role electron donor-acceptor interactions play in the nucleophilic alkyl transfer. Phenyl- and alkyl-substituted borate ions form highly colored charge-transfer salts with a variety of cationic pyridinium acceptors [65], which represent ideal substrates to probe the methyl-transfer mechanisms. Most pyridinium borate salts are quite stable in crystalline form (see for example Figure 5C), but decompose rapidly when dissolved in tetrahydrofuran to yield methylated hydropyridines (Eq. 65). 

Mechanistic studies have been reported on the addition of alkylphosphonic acid reagents (325) to trialkyl-substituted epoxides (326). The addition occurs according to a three-step mechanism starting with rapid nucleophilic attack of the phosphorylated anion on the most alkyl-substituted carbon of oxirane, followed by formation of a dioxaphospholane structure (327) with release of... 

Although the mechanism is not understood, evidence strongly suggests this much the alkyl group R is transferred from copper, taking a pair of electrons with it, and attaches itself to the alkyl group R by pushing out halide ion (nucleophilic aliphatic substitution. Sec. 14.9). 

This duality of mechanism does not reflect exceptional behavior, but is usual for electrophilic aromatic substitution. It also fits into the usual pattern for nucleophilic aliphatic substitution (Sec. 14.16), which—from the standpoint of the alkyl halide—is the kind of reaction taking place. Furthermore, the particular halides (T and methyl) which appear to react by this second mechanism are just the ones that would have been expected to do so. 

In following sections, we shall discuss the mechanisms of nucleophilic aliphatic substitution and of elimination using alkyl halides as our examples. But we should realize that these reactions take place in exactly the same ways with a variety of other compounds compounds which, like alkyl halides, contain good leaving groups. 

We take up the aryl halides in a separate chapter because they differ so much from the alkyl halides in their preparation and properties. Aryl halides as a class are comparatively unreactive toward the nucleophilic substitution reactions so characteristic of the alkyl halides. The presence of certain other groups on the aromatic ring, however, greatly increases the reactivity of aryl halides in the absence of such groups, reaction can still be brought about by very basic reagents or high temperatures. We shall find that nucleophilic aromatic substitution can follow two very different paths the bimolecular displacement mechanism for activated aryl halides and the elimination-addition mechanismy which involves the remarkable intermediate called benzyne. 

This type of cyclopropane formation only occurs when a-alkyl-substituted malonates (R = alkyl) are used as nucleophile (entries 5, 6 and 7). The mechanism is not known. 

The two mechanisms for Friedel-Crafts alkylation are not dissimilar to the two mechanisms for nucleophilic aliphatic substitution. In an S,j1 mechanism, a carbocation is generated from an alkyl halide before the nucleophile attacks, but in an S 2 reaction the halide departs simultaneously with the nucleophile attacking the R group. In the Friedel-Crafts reaction, benzene behaves as the nucleophile. 

---