Electrophiles carbocations

The ionization mechanism for nucleophilic substitution proceeds by rate-determining heterolytic dissociation of the reactant to a tricoordinate carbocation (also sometimes referred to as a carbonium ion or carbenium ion f and the leaving group. This dissociation is followed by rapid combination of the highly electrophilic carbocation with a Lewis base (nucleophile) present in the medium. A two-dimensional potential energy diagram representing this process for a neutral reactant and anionic nucleophile is shown in Fig. 

We call the carbocation, which exists only transiently during the course of the multistep reaction, a reaction intermediate. As soon as the intermediate is formed in the first step by reaction of ethylene with H+, it reacts further with Br in a second step to give the final product, bromoethane. This second step has its own activation energy (AG ), its own transition state, and its own energy change (AG°). We can picture the second transition state as an activated complex between the electrophilic carbocation intermediate and the nucleophilic bromide anion, in which Br- donates a pair of electrons to the positively charged carbon atom as the new C-Br bond starts to form. 

Carbocations are common intermediates in organic reactions. Highly substituted alkyl halides can ionize when they are heated in a polar solvent. The strongly electrophilic carbocation reacts with any available nucleophile, often the solvent. 

An alkyl chloride, plus an AICI3 catalyst, produces an electrophilic carbocation. 

There is no quantitative information on the enthalpies of Reaction (55) in solution for unstabilized carbocations. The only available information concerns highly stabilized carbocations. It may be expected that the enthalpy of carbenium-onium ion interconversion in solution will be lower than in the gas phase, because more electrophilic carbocations will be solvated more strongly than onium ions. The magnitude of this effect is illustrated by the data of Table 5. 

Earlier we mentioned the Wurtz reaction as being one of the simplest approaches to the formation of C-C bonds. In this reaction, the alkyl halide serves as the electrophile (carbocation equivalent) and the organometallic derivative plays the role of the nucleophile (carbanion equivalent). We have also seen that this old reaction has recently become a feasible route for the creation of C-C bonds due... 

Like other electrophiles, carbocations add to alkenes to form new carbocations, which can then undergo substitution or elimination, depending on the reaction conditions. 

With 2° and 3° RCI, the Lewis acid-base complex reacts further to give a 2° or 3° carbocation, which serves as the electrophile. Carbocation formation occurs only with 2° and 3° alkyl chlorides, because they afford more stable carbocations. 

The electrophilic carbocation, 4-27, reacts with nucleophilic water. Because water is present in large excess over ethanol, this reaction occurs preferentially and shifts the equilibrium toward the hydrolysis product. The proto-nated intermediate loses a proton to give 4-28. 

Nucleophilic reaction of formic acid at the electrophilic carbocation can be either cis or trans to the phenyl group in the bicyclic intermediate and leads to the two products. 

The 77 electrons in a C=C 77 bond can react with a Lewis acidic electrophile to give a carbocation. The simplest example is the reaction of an alkene with H+. Note that one of the C atoms of the 77 bond forms the bond to H+ using the electrons of the 77 bond, whereas the other C becomes electron-deficient and gains a formal positive charge. Other cationic electrophiles (carbocations, acylium ions, and Br+) can react with C=C 77 bonds too. 

An alkene is an average electron source, and an aromatic compound is usually worse therefore to get electrophilic addition to alkenes and aromatic compounds to occur one needs a good electron sink. Often a loose association of an electrophile with the pi electron cloud (called a pi-complex) occurs before the actual sigma bond formation step. The best electrophiles, carbocations, add easily. For an overview of electrophilic additions to alkenes, see Section 4.4. 

Aromatic chemicals are metabolized into unstable arene-oxides, which, as epoxides, are comparable to potentially equivalent electrophilic carbocations. These metabolites react easily with thiol groups derived from proteins, leading, for example, to hepatotoxicity. Bromobenzene seems to target a large group of functionally diverse hepatic proteins, as demonstrated recently in a proteomic analysis. The chemical is oxidized (Figure 33.10) into a 3,4-epoxide, which... 

The concept of metabolic activation developed with AAF was then apphed to PAHs, aflatoxins, nitrosamines, nitrosoureas, hydrazines, urethane, and vinyl chloride. Several metabolic activation schemes are presented in Figure 6.2. In each case a highly reactive electrophilic carbocation is formed. We now know that the concept of metabolic activation applies to many genotoxic carcinogens and helps to explain... 

The (OTcial electronic interaction is between an unshared electron pair of the nucleophilic chloride anion and the vacant 2p orbital of the electrophilic carbocation. 

The Friedel-Crafts acylation, the reaction of an aromatic compound with an acid chloride and a Lewis acid (such as AICI3), adds an acyl group to the aromatic ring to give an aromatic ketone product. like the previously discussed alkylation reaction, it involves a strongly electrophilic carbocation (called an acylium ion), but this carbocation is not subject to rearrangement since it is stabilized by resonance. 

The generation of the appropriate electrophile (carbocation, carbocation complex, or acylium ion) in the presence of an aromatic ring system (nucleophile) can lead to alkylation or acylation of the aromatic ring. This set of reactions, discovered by Charles Friedel and James Crafts in 1877, originally used aluminum chloride as the catalyst. The reaction is now known to be cat-al) ed by a wide range of Lewis acids, including ferric chloride, zinc chloride, boron trifluoride, and strong acids, such as sulfuric, phosphoric, and hydrofluoric acids. 

Both chiral Brpnsted and Lewis acids have been useful in asymmetric Friedel-Crafts reactions. For example, the chiral Brpnsted acid 40 was used in the asymmetric synthesis of chiral fluorenes from an achiral indole and the biarylaldehyde 39 (Scheme 1.11) [32]. Initial steps in the conversion lead to the ion pair 42. Through ion pairing with the electrophilic carbocation, the chiral anion... 

A concise synthesis of the indole alkaloid ( )-actinophyllic acid was reported, in which a key step involves a cationic reaction cascade. The indole (163) is treated with TMSOTf to generate the electrophilic carbocation (164), and this reacts with a dihydroazepine to provide the A-acyliminium ion intermediate (166). A Eriedel-Crafts reaction gives the indole product (165) and the framework for actinophyllic acid (Scheme 34). 

Like other electrophiles, carbocations add to alkenes to form new carbocations, which can then undergo substitution or elimination reactions depending on the reaction conditions. With this in mind, consider the following reactions of nerol, a natural product isolated from lemon grass and other plant sources. Treatment of nerol with TsOH forms a-terpineol as the major product, whereas treatment of nerol with chlorosulfonic acid, HSO3CI, forms a constitutional isomer, a-cyclogeraniol. Write stepwise mechanisms for both processes. Each mechanism involves the addition of an electrophile—a carbocatlon— to a double bond. 

The 7C bond fimctions as a nucleophile and attacks the electrophilic carbocation. This step is therefore a nucleophilic attack. 

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