Electrophilic participation

A reaction in which an electrophile participates in het-erolytic substitution of another molecular entity that supplies both of the bonding electrons. In the case of aromatic electrophilic substitution (AES), one electrophile (typically a proton) is substituted by another electron-deficient species. AES reactions include halogenation (which is often catalyzed by the presence of a Lewis acid salt such as ferric chloride or aluminum chloride), nitration, and so-called Friedel-Crafts acylation and alkylation reactions. On the basis of the extensive literature on AES reactions, one can readily rationalize how this process leads to the synthesis of many substituted aromatic compounds. This is accomplished by considering how the transition states structurally resemble the carbonium ion intermediates in an AES reaction. 

Trivalent carbenium ions are the key intermediates in electrophilic reactions of Tt-donor unsaturated hydrocarbons. At the same time, pen-tacoordinated carbonium ions are the key to electrophilic reactions of cr-donor saturated hydrocarbons through the ability of C-H or C-C single bonds to participate in carbonium ion formation. 

Various other heteroatom-substituted earbocations were also found to be activated by superacids. a-Nitro and a-cyanocarbenium ions, R2C N02 or R2C CN, for example, undergo O- or N-protonation, respectively, to dicationic species, decreasing neighboring nitrogen participation, which greatly enhances the electrophilicity of their carbo-... 

There were two schools of thought concerning attempts to extend Hammett s treatment of substituent effects to electrophilic substitutions. It was felt by some that the effects of substituents in electrophilic aromatic substitutions were particularly susceptible to the specific demands of the reagent, and that the variability of the polarizibility effects, or direct resonance interactions, would render impossible any attempted correlation using a two-parameter equation. - o This view was not universally accepted, for Pearson, Baxter and Martin suggested that, by choosing a different model reaction, in which the direct resonance effects of substituents participated, an equation, formally similar to Hammett s equation, might be devised to correlate the rates of electrophilic aromatic and electrophilic side chain reactions. We shall now consider attempts which have been made to do this. 

Experimental requirements for the isolation of these nitramino derivatives are developed in Ref. 87. They rearrange easily to ring nitro-substituted isomers (see Section V.6). In the 2-aminothiazole series, nitration may proceed through direct electrophilic substitution competing with rearrangement of nitramino derivatives. Dickey et al. have shown that the rearrangement proceeds rapidly in 96% sulfuric acid at 2(fC, but in 85% sulfuric add it is very slow so. according the concentration of add various mechanisms can participate in the formation of the 5-nitro derivative. 

Reactions of the Aromatic Ring. The aromatic ring of hydroxybenzaldehydes participates in several typical aromatic electrophilic reactions. Ha.logena.tlon, Chlorination and bromination yield mono- and dihalo derivatives, depending on reaction conditions. Bromination of / -hydroxy-benzaldehyde in chloroform yields 65—75% of the product shown (39). 

The quiaones have excellent redox properties and are thus important oxidants ia laboratory and biological synthons. The presence of an extensive array of conjugated systems, especially the a,P-unsaturated ketone arrangement, allows the quiaones to participate ia a variety of reactioas. Characteristics of quiaoae reactioas iaclude nucleophilic substitutioa electrophilic, radical, and cycloaddition reactions photochemistry and normal and unusual carbonyl chemistry. 

The hydroxyben2oic acids have both hydroxyl and the carboxyl groups and, therefore, participate in chemical reactions characteristic of each of these moieties. In addition, these acids can undergo electrophilic ring substitution. The following reactions are discussed in terms of saUcyhc acid, but are characteristic of all the hydroxyben2oic acids. 

The positive bromine which leads to bromonium ion intermediates is softer and also has unshared electron pairs which can permit a total of four electrons to participate in the bridged bromonium ion intermediate. This would be expected to lead to a more strongly bridged and more stable species than is possible in the case of the proton. The bromonium ion can be represented as having two covalent bonds to bromine and is electrophilic but not electron-deficient. 

The transition state for the rapid hydrolysis of the monoanion has been depicted as involving an intramolecular general acid catalysis by the carboxylic acid group, with participation by the anionic carboxylate group, which becomes bound at the developing electrophilic center... 

Other, closely related, nicotinic acid derivatives and the unsubstituted system itself have also been studied and undergo similar reactions. Moreover, the approach may be extended to 2,2 -bipyridyls. Newkome and his collaborators have used the 2,2 -bipyridyl unit 19) as an electrophile in which ortho-hr ommes served as leaving groups. They have also used halomethyl systems and formed the macrocycles from these systems . A compound derived from the latter starting material 20) is reported to form a cobalt complex, in which both nitrogens and only one of the oxygen atoms participate in the binding . The two precursor units are shown below as 79 and 20, respectively. 

Resonance stabilization in the products is best illustrated by the reactant anhydrides (Figure 3.10b). The unpaired electrons of the bridging oxygen atoms in acetic anhydride (and phosphoric anhydride) cannot participate in resonance structures with both electrophilic centers at once. This competing resonance situation is relieved in the product acetate or phosphate molecules. 

The aminobutynones 342 contain a push-pull system with a strongly electron-withdrawing carbonyl group therefore, they show electrophilic properties. Cyclizations with their participation proceed differently from those with ynamines (91UK103 00UK642) and acetylenic ketones (73UK511). 

Vinyl radicals can also participate in 6-exo cyclizations. In pioneering work, Stork and his group at Columbia University showed that stereoisomeric vinyl bromides 20 and 21 (see Scheme 3) can be converted to cyclohexene 22.7 The significance of this finding is twofold first, the stereochemistry of the vinyl bromide is inconsequential since both stereoisomers converge upon the same product and second, the radical cyclization process tolerates electrophilic methoxycarbonyl groups. The observation that the stereochemistry of the vinyl bromide is inconsequential is not surprising because the barrier for inversion of most vinyl radicals is very low.8 This important feature of vinyl radical cyclization chemistry is also exemplified in the conversion of vinyl bromide 23 to tricycle 24, the key step in Stork s synthesis of norseychellanone (25) (see Scheme 4).9 As in... 

Ketal 73 can be formed in a yield of about 60 % by refluxing a solution of tetronic acid (36), ethylene glycol, and a catalytic amount of para-toluenesulfonic acid in benzene for approximately 12 hours. With only one electrophilic site, 73 reacts smoothly with Dibal-H to give lactol 35 in 84% yield. Compound 35, a participant in a ring-chain tautomeric equilibrium process,18 should be regarded as a latent aldehyde. This substance can, in fact, serve as... 

In the direct coupling reaction (Scheme 30), it is presumed that a coordinatively unsaturated 14-electron palladium(o) complex such as bis(triphenylphosphine)palladium(o) serves as the catalytically active species. An oxidative addition of the organic electrophile, RX, to the palladium catalyst generates a 16-electron palladium(n) complex A, which then participates in a transmetalation with the organotin reagent (see A—>B). After facile trans- cis isomerization (see B— C), a reductive elimination releases the primary organic product D and regenerates the catalytically active palladium ) complex. 

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