Electrophilic addition reactions base mechanism

Before beginning a detailed discussion of alkene reactions, let s review briefly some conclusions from the previous chapter. We said in Section 5.5 that alkenes behave as nucleophiles (Lewis bases) in polar reactions. The carbon-carbon double bond is electron-rich and can donate a pair of electrons to an electrophile (Lewis acid), for example, reaction of 2-methylpropene with HBr yields 2-bromo-2-methylpropane. A careful study of this and similar reactions by Christopher Ingold and others in the 1930s led to the generally accepted mechanism shown in Figure 6.7 for electrophilic addition reactions. 

When excess alkene is employed, the addition of the hypohalite to the alkene takes place more readily than the above-mentioned substitutive electrophilic dehalogenation reaction. Based on the structures of stereoisomers obtained from the reactions of hypochlorite with cis- and trans-CHF=CHF and trans-CHC =CllC a regio- and stereospecific syn-addition mechanism was suggested (equation 76). Methyl and trifluoromethyl esters of... 

Benzene s aromaticity causes it to undergo electrophilic aromatic substitution reactions. The electrophilic addition reactions characteristic of alkenes and dienes would lead to much less stable nonaromatic addition products. The most common electrophilic aromatic substitution reactions are halogenation, nitration, sulfonation, and Friedel-Crafts acylation and alkylation. Once the electrophile is generated, all electrophilic aromatic substitution reactions take place by the same two-step mechanism (1) The aromatic compound reacts with an electrophile, forming a carbocation intermediate and (2) a base pulls off a proton from the carbon that... 

The azo coupling reaction proceeds by the electrophilic aromatic substitution mechanism. In the case of 4-chlorobenzenediazonium compound with l-naphthol-4-sulfonic acid [84-87-7] the reaction is not base-catalyzed, but that with l-naphthol-3-sulfonic acid and 2-naphthol-8-sulfonic acid [92-40-0] is moderately and strongly base-catalyzed, respectively. The different rates of reaction agree with kinetic studies of hydrogen isotope effects in coupling components. The magnitude of the isotope effect increases with increased steric hindrance at the coupler reaction site. The addition of bases, even if pH is not changed, can affect the reaction rate. In polar aprotic media, reaction rate is different with alkyl-ammonium ions. Cationic, anionic, and nonionic surfactants can also influence the reaction rate (27). 

Both steps in this general mechanism are based on precedent. It is called electrophilic addition because the reaction is triggered by the attack of an acid acting as an electrophile on the tt electrons of the double bond. Using the two tt electrons to fonn a bond to an electrophile generates a carbocation as a reactive intennediate normally this is the rate-detennining step. 

Limonene, a fragrant hydrocarbon found in lemons and oranges, is bio-synthesized from geranyl diphosphate by the following pathway. Add curvec arrows to show the mechanism of each step. Which step involves an alkene electrophilic addition (The ion 0P2064- is the diphosphate ion, and "Base is an unspecified base in the enzyme that catalyzes the reaction.)... 

Based on what we ve seen thus far, a possible mechanism for the reaction of bromine with alkenes might involve electrophilic addition of Br+ to the alkene, giving a carbocation that could undergo further reaction with Br- to yield the dibromo addition product. 

The mechanism through which catalytic metal carbene reactions occur is outlined in Scheme 2. With dirhodium(II) catalysts the open axial coordination site on each rhodium serves as the Lewis acid center that undergoes electrophilic addition to the diazo compound. Lewis bases that can occupy the axial coor-... 

The first step, as we have already seen (12-3), actually consists of two steps. The second step is very similar to the first step in electrophilic addition to double bonds (p. 970). There is a great deal of evidence for this mechanism (1) the rate is first order in substrate (2) bromine does not appear in the rate expression at all, ° a fact consistent with a rate-determining first step (3) the reaction rate is the same for bromination, chlorination, and iodination under the same conditions (4) the reaction shows an isotope effect and (5) the rate of the step 2-step 3 sequence has been independently measured (by starting with the enol) and found to be very fast. With basic catalysts the mechanism may be the same as that given above (since bases also catalyze formation of the enol), or the reaction may go directly through the enolate ion without formation of the enol ... 

Although the reaction of ketones and other carbonyl compounds with electrophiles such as bromine leads to substitution rather than addition, the mechanism of the reaction is closely related to electrophilic additions to alkenes. An enol, enolate, or enolate equivalent derived from the carbonyl compound is the nucleophile, and the electrophilic attack by the halogen is analogous to that on alkenes. The reaction is completed by restoration of the carbonyl bond, rather than by addition of a nucleophile. The acid- and base-catalyzed halogenation of ketones, which is discussed briefly in Section 6.4 of Part A, provide the most-studied examples of the reaction from a mechanistic perspective. 

The mechanisms for metal-catalyzed and organocatalyzed direct aldol addition reactions differ one from another, and resemble the mode of action of the type 11 and type I aldolases, respectively. Some metal-ligand complexes, for example, 1-4 and 9 are considered to have a bifunctional character [22], embodying within the same molecular frame a Lewis acidic site and a Bronsted basic site. Whereas base would be required to form the transient enolate species as an active form of the carbonyl donor, the Lewis acid site would coordinate the acceptor aldehyde carbonyl, increasing its electrophilicity. By this means, both transition state stabilization and substrates preorganization would be provided (see Scheme 5 for a proposal). 

Although these additions to CO double bonds have some superficial similarities to the electrophilic additions to CC double bonds that were presented in Chapter 11, there are many differences. The acidic conditions mechanism here resembles the mechanism for addition to carbon-carbon double bonds in that the electrophile (the proton) adds first, followed by addition of the nucleophile. However, in this case the first step is fast because it is a proton transfer involving oxygen, a simple acid-base reaction. The second step, the attack of the nucleophile, is the rate-determining step. (Recall that it is the first step, the addition of the electrophile, that is slow in the additions to CC double bonds.) Furthermore, in the case of additions to simple alkenes there is no mechanism comparable to the one that operates here under basic conditions, in which the nucleophile adds first. Because the nucleophile adds in the slow step, the reactions presented in this chapter are termed nucleophilic additions, even if the protonation occurs first. In... 

The mechanism of electrophilic addition consists of two successive Lewis acid-base reactions. In Step [1], the alkene is the Lewis base that donates an electron pair to H-Br, the Lewis acid, while in Step [2], Br is the Lewis base that donates an electron pair to the carbocation, tbe Lewis acid. 

In bromination (Mechanism 18.2), the Lewis acid FeBr3 reacts with Br2 to form a Lewis acid-base complex that weakens and polarizes the Br- Br bond, making it more electrophilic. This reaction is Step [1] of the mechanism for the bromination of benzene. The remaining two steps follow directly from the general mechanism for electrophilic aromatic substitution addition of the electrophile (Br in this case) forms a resonance-stabilized carbocation, and loss of a proton regenerates the aromatic ring. 

All the electrophilic aromatic substitutions shown in reaction 3 of Review Table 3 occur by the same two-step mechanism. The first step is similar to the first step in electrophilic addition to alkenes An electron-poor reagent reacts with the electron-rich aromatic ring. The second step is identical to what happens during E2 elimination A base abstract a hydrogen atom next to the positively charged carbon, and elimination of the proton occurs. 

Under catalysis by fluoride ions, tert-butylate or other Lewis bases [70], McjSiCLj can transfer "CLj equivalents in high yields to a large variety of electrophilic substrates. The mechanism of this transfer involves the formation of carbanionoid alkoxy trimethyl trifluoromethyl siliconate species, which add their trifluoromethyl moiety to carbonyl groups in a self-activating chain reaction which is initiated by a small amount of fluoride ions (5-10 mol%) [65] (Scheme 2.127). Some of the intermediate siliconate species have been isolated and characterized either by NMR or X-ray crystallography [71, 72]. Remarkably, in contrast with most other organosilicon reagents the addition reaction cannot be initiated by Lewis acid catalysts. 

---