Electrophiles secondary

Compound Acetal or Ether Solvent Nuc." Temp. (°C) Electrophile Secondary Site Terminal Site Ref. 

Alkyl halides by themselves are insufficiently electrophilic to react with benzene Aluminum chloride serves as a Lewis acid catalyst to enhance the electrophihcity of the alkylating agent With tertiary and secondary alkyl halides the addition of aluminum chlonde leads to the formation of carbocations which then attack the aromatic ring... 

Secondary alkyl halides react by a similar mechanism involving attack on benzene by a secondary carbocation Methyl and ethyl halides do not form carbocations when treated with aluminum chloride but do alkylate benzene under Friedel-Crafts conditions The aluminum chloride complexes of methyl and ethyl halides contain highly polarized carbon-halogen bonds and these complexes are the electrophilic species that react with benzene... 

The polymerization of ethyleneimine (16,354—357) is started by a catalyticaHy active reagent (H or a Lewis acid), which converts the ethyleneimine into a highly electrophilic initiator molecule. The initiator then reacts with nitrogen nucleophiles, such as the ethyleneimine monomer and the subsequendy formed oligomers, to produce a branched polymer, which contains primary, secondary, and tertiary nitrogen atoms in random ratios. Termination takes place by intramolecular macrocycle formation. 

A tertiary carbonium ion is more stable than a secondary carbonium ion, which is in turn more stable than a primary carbonium ion. Therefore, the alkylation of ben2ene with isobutylene is much easier than is alkylation with ethylene. The reactivity of substituted aromatics for electrophilic substitution is affected by the inductive and resonance effects of a substituent. An electron-donating group, such as the hydroxyl and methyl groups, activates the alkylation and an electron-withdrawing group, such as chloride, deactivates it. 

Other carbon electrophiles which are frequently employed include aldehydes, ketones, esters, nitriles and amides of the type RCONMei. An indirect method of acylation involves the initial reaction of a lithio compound with an aldehyde followed by oxidation of the resulting secondary alcohol to the corresponding acyl derivative. 

We learned in the preceding section that different reactions are observed when the various classes of alkylamines—primary, secondary, and tertiary—react with nitrosating agents. Although no useful chemistr-y attends the nitrosation of tertiar y alkylamines, electrophilic aromatic substitution by nitrosyl cation ( n Q ) takes place with A,A-dialkyl-arylfflnines. 

In 1974, Hegedus and coworkers reported the pa]ladium(II)-promoted addition of secondary amines to a-olefins by analogy to the Wacker oxidation of terminal olefins and the platinum(II) promoted variant described earlier. This transformation provided an early example of (formally) alkene hydroamination and a remarkably direct route to tertiary amines without the usual problems associated with the use of alkyl halide electrophiles. 

When an unsymmetrically substituted vinyl monomer such as propylene or styrene is polymerized, the radical addition steps can take place at either end of the double bond to yield either a primary radical intermediate (RCH2-) or a secondary radical (R2CH-). Just as in electrophilic addition reactions, however, we find that only the more highly substituted, secondary radical is formed. 

How can we account for the formation of 1,4-addition products The answer is that allylic carbocations are involved as intermediates (recall that allylic means "next to a double bond"). When 1,3-butadiene reacts with an electrophile such as H+, two carbocation intermediates are possible a primary nonal-lylic carbocation and a secondary allylic cation. Because an allylic cation is stabilized by resonance between two forms (Section 11.5), it is more stable and forms faster than a nonallylic carbocation. 

The mechanism of the alkoxymercuration reaction is similar to that described in Section 7.4 for hvdroxymercuration. The reaction is initiated by electrophilic addition of Iig2+ to the alkene, followed by reaction of the intermediate cation with alcohol and reduction of the C-Hg bond by NaBH4. A variety of alcohols and alkenes can be used in the alkoxymercuration reaction. Primary, secondary, and even tertiary alcohols react well, but ditertiary ethers can t be prepared because of steric hindrance to reaction. 

The general features of this elegant and efficient synthesis are illustrated, in retrosynthetic format, in Scheme 4. Asteltoxin s structure presents several options for retrosynthetic simplification. Disassembly of asteltoxin in the manner illustrated in Scheme 4 furnishes intermediates 2-4. In the synthetic direction, attack on the aldehyde carbonyl in 2 by anion 3 (or its synthetic equivalent) would be expected to afford a secondary alcohol. After acid-catalyzed skeletal reorganization, the aldehydic function that terminates the doubly unsaturated side chain could then serve as the electrophile for an intermolecular aldol condensation with a-pyrone 4. Subsequent dehydration of the aldol adduct would then afford asteltoxin (1). 

A reasonable mechanism is shown in equation 23 methyllithium attacks the sulfur atom, giving the secondary carbanion 36 by cleavage of the four-membered ring. A rapid proton transfer produces the sulfonyl-stabilized carbanion 37 which reacts with the added electrophile to give the product (equation 23)3. 

Apart from a few studies (ref. 7), the use of deuterium kinetic isotope effects (kie s) appears to have had limited use in mechanistic studies of electrophilic bromination of olefins. Secondary alpha D-kie s have been reported for two cases, trans-stilbene fi and p-substituted a-d-styrenes 2, these giving relatively small inverse kie s of... 

Among the peculiar features of 2-bromoamides there are the following i) possibility of substitution at the tertiary C-Br (RCO2H, RR NH, or a saccharide, as the nucleophiles) ii) chiral stability and stereochemical control at the secondary C-Br atom (RR NH, ROH or a saccharide as the nucleophiles) iii) the presence of bromine allows cyclic voltammetry and electroreduction at controlled potential both of starting compounds and relevant intermediates iv) the Ca polarity can be reversed upon electroreduction, and the resulting Ca enolate forms a C-C bond (CO2 as the electrophile). 

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