Structure of the Electrophile

Reaction of allylic silanes with enantiomerically pure 1,3-dioxanes has been found to proceed with high enantioselectivity.70 The enantioselectivity is dependent on several reaction variables, including the Lewis acid and the solvent. The observed stereoselectivity appears to reflect differences in the precise structure of the electrophilic species that is generated. Mild Lewis acids tend to react with inversion of configuration at the reaction site, whereas very strong Lewis acids cause loss of enantioselectivity. These trends, and related effects of solvent and other experimental variables, determine the nature of the electrophile. With mild Lewis acids, a tight ion pair favors inversion, whereas stronger... 

Again, the transition state may not always be six-centered (as in equation (16)) and it is obviously possible for seven- or eight-centred transition states to be formed if the structure of the electrophile so permitted. 

Metalated enones and related compounds are usually alkylated at the position a to the electron-withdrawing group [109-113], but the precise structure of the electrophile can also have an impact on regioselectivity (Scheme5.10). Certain substrates, such as crotonic acid dianions [111], crotonamide dianions [114, 115], or certain enones [116] can also give mixtures of a- and y-alkylatcd products, whereas metalated -oxy [117-119] or /i-amino [120, 121] acrylic acid derivatives often yield pure products of y-alkylation. 

Allylic and propargylic heteroatom-substituted carbanions can yield rearranged or unrearranged products on treatment with an electrophile. The regio- and stereoselectivity of these reactions depends on the precise structure of the carbanion, on the metal and solvent chosen [199], and on the structure of the electrophile [150, 200-203], and can be difficult to predict. 

All of the electrophilic aromatic substitution reactions follow this same general mechanism. The only difference is the structure of the electrophile and how it is generated. Let s look at a specific example, the nitration of benzene. This reaction is accomplished by reacting benzene with nitric acid in the presence of sulfuric acid ... 

Ambident ions containing a second row element as one of the nucleophilic atoms also give different reaction products depending on the structure of the electrophile as shown by the following examples ... 

The second factor that determines whether substitution or elimination occurs is the structure of the electrophile. 

Fig. 13.11 Structures of the electrophilic motif of the HAL active site (A) and the GFP chromophore (B).

This mechanism implies that a considerable change in the structure of the electrophile occurs prior to a-bond formation. These structural changes could account in large part for the energy barrier to formation of the ct complex. Moreover, this mechanism implies that the cation radical-radical pair might play a key role in determining the isomeric ortho, meta, para) product composition. These issues have been investigated most closely for nitration and bromination and are consider further when those reactions are discussed. 

You may be wondering how the reaction of Eq. 11.44 differs in practice from an 5 2 reaction, and indeed Pross and Shaik propose that many "normal" 5 2 reactions are instead single-step SET reactions. Therefore, Scheme 11.8 represents a limiting case for a pure SET reaction, while Eq. 11.44 shows an alternative view of a classic Sn2 reaction. These are subtle distinctions, as we are considering exactly how an electron moves from one center to another. This may be a risky proposition for an inherently quantum mechanical object like an electron, but it does explain the results found for some reactions. We can imagine a continuum of possible intermediate mechanisms depending upon the structure of the electrophile, nucleophile, and solvent. 

In this case, there are two curved arrows. The first shows the nucleophile attacking the electrophile, but what is the function of the second curved arrow There are a couple of ways to view this second curved arrow. We can simply think of it as a resonance arrow We can imagine first drawing the resonance structure of the electrophile and then having the nucleophile attack ... 

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