Nucleophilic substitution reactions elucidating mechanisms

The mechanisms of phosphoryl-group transfer reactions have been elucidated through studies on nucleophilic substitution reactions at phosphorus. 

In the elucidation of reaction mechanisms in organic chemistry, stereochemical investigations played an extremely important role. In their classical studies in the 1930 s, Ingold and Hughes showed that in nucleophilic substitution reactions either... 

The direct nucleophilic substitution reactions (Scheme 2) [16-22], restricted mainly to n-activated alcohols such as secondary arylmethanols, allylic and propargylic alcohols, and tertiary alcohols that can readily form stable carbocationic intermediates, are mechanistically different to hydrogen autotransfer reactions. Although these reactions are not the focus of this chapter, since they are also very relevant research areas, this brief introduction is anticipated to provide potentially helpful references to assist interested researchers in their studies, especially in boardline research where elucidation of reaction mechanisms is difficult. 

The typical reactions of carbocation intermediates were discussed in Chapter 7. The solvolysis of alkyl halides is an example of the involvement of carbocations in the SnI mechanism, in other words, where the final outcome is a nucleophilic substitution. The first step is a heterolytic cleavage of the C—X bond. Properties of X which favor heterolytic cleavage, namely electronegativity difference with carbon (the larger, the better) and the degree of overlap of the X orbital with the spn orbital of carbon (the smaller the better), have already been elucidated (Chapter 4). The transition state has partial... 

The mechanism of the amines or alcohols arylation catalyzed by nickel(II) complexes has not been elucidated until now (refs. 7, 17), even though the arylation of nucleophiles catalyzed by nickel(0) complexes is better understood. In this last case it is generally admitted that the reaction proceeds by an oxidative addition step, followed by a nucleophilic substitution, and then a reductive elimination of the arylation product (Scheme 4). According to the work of Kochi (ref. 18), the oxidative addition of the haloarene on a nickel(O) complex takes place through a monoelectronic transfer from the metal to the aryl halide with simultaneous formation of a nickel(I) intermediate, the actual catalyst of the reaction (ref. 6). 

Much effort has been devoted to the theoretical elucidation of the mechanism of nucleophilic substitution at silicon. The calculations tried to answer two major questions (1) Does substitution occur by a one-step reaction via transition state 177 or by a two-step process via intermediate 178 (equation 58 where Nu = nucleophile, LG = leaving group) (2) What is the stereochemistry of the substitution and what are the factors which control it ... 

Substitutions by the SRn 1 mechanism (substitution, radical-nucleophilic, unimolecular) are a well-studied group of reactions which involve SET steps and radical anion intermediates (see Scheme 10.4). They have been elucidated for a range of precursors which include aryl, vinyl and bridgehead halides (i.e. halides which cannot undergo SN1 or SN2 mechanisms), and substituted nitro compounds. Studies of aryl halide reactions are discussed in Chapter 2. The methods used to determine the mechanisms of these reactions include inhibition and trapping studies, ESR spectroscopy, variation of the functional group and nucleophile reactivity coupled with product analysis, and the effect of solvent. We exemplify SRN1 mechanistic studies with the reactions of o -substituted nitroalkanes (Scheme 10.29) [23,24]. 

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