Carbon electrophilic methylations

The only doubtful case is the secondaiy alkyl derivative, which can react by either mechanism, though it is not very good at either. The first question you should ask when faced with a new nucleophilic substitution is Is the carbon electrophile methyl, primary, secondaiy, or tertiary This will start you off on the right foot, which is why we introduced these important structural terms in Chapter 2. 

The dianions of methylated thiophenecarboxylic acids e.g. 155) are also readily generated by reaction with LDA they undergo preparatively useful reactions with a range of carbon electrophiles (80JOC4528). 

An optically active sulfoxide may often be transformed into another optically active sulfoxide without racemization. This is often accomplished by formation of a new bond to the a-carbon atom, e.g. to the methyl carbon of methyl p-tolyl sulfoxide. To accomplish this, an a-metallated carbanion is first formed at low temperature after which this species may be treated with a large variety of electrophiles to give a structurally modified sulfoxide. Alternatively, nucleophilic reagents may be added to a homochiral vinylic sulfoxide. Structurally more complex compounds formed in these ways may be further modified in subsequent steps. Such transformations are the basis of many asymmetric syntheses and are discussed in the chapter by Posner and in earlier reviews7-11. 

In a similar fashion 2-aminothiophenol can be reacted with 1,3-bis carbon electrophiles to give various types of 1,5-benzothiazepine. Thus the benzo analogues of (408) and (409), e.g. (410), are prepared by parallel routes, reaction with 1,3-diphenylpropynone gives (411), reaction with /3-ketoesters gives products of type (412), reaction with diketene gives (413), and the reaction with methyl 3-arylglycidates gave (414) which could not be dehydrated. 

Reactions of acyclic derivatives with carbon electrophiles have also been examined.33,34 An illustrative reaction involving methylation of the unsubstituted complex [MnCr 4-butadiene)(CO)3], (19), is shown in Scheme 16. Again, the reaction is presumed to occur via a methylmanganese species (20) and after methyl migration the unsaturated metal center is stabilized by formation of a Mn—H—C bridge (isomers 21a and 21b). Deprotonation of equilibrating (21a and 21b) yields the [Mn(l-methylbutadiene)(CO>3]-complex (22), which has exclusively trans stereochemistry.34 This sequence represents alkylation of the terminal carbon of butadiene and complements the iron carbonyl chemistry, where terminal acylation has been achieved as described above. Unpublished results indicate that a second methylation of (22) occurs... 

Although methyl 2-siloxycyclopropanecarboxylates are cleaved by certain electrophiles, only tetracyanoethylene (TCNE) as a carbon electrophile could directly be added to phenyl or vinyl activated cyclopropanes providing cyclopentane derivatives 61). 

You can see that the rate of the SN2 reaction decreases dramatically each time one of the hydrogens on the electrophilic carbon of methyl chloride is replaced with a... 

Identify the leaving group, the electrophilic carbon (the one bonded to the leaving group), the nucleophile, and the solvent (usually over the arrow). If the electrophilic carbon is methyl or a simple primary carbon, the mechanism is SN2. If the electrophilic carbon is tertiary, the mechanism is SN1. If the electrophilic carbon is secondary, allylic, or benzylic, you must examine the nucleophile and the solvent. With good nucleophiles, the mechanism is SN2. (Aprotic solvents make the nucleophile even stronger.) With poor nucleophiles and polar solvents, the mechanism is SN1. 

The carbon (blue) bonded to the hydroxy group in the alcohol comes from the carbonyl carbon electrophile of the starting material. This carbon is also bonded to a methyl group and an ethyl group. We can add the ethyl group, using the reaction of ethylmag-... 

But that is not our only option. The reactivity and hence the structure of the carbon electrophile matter too. If we want reaction at a methyl group we can t change the carbon skeleton, but we can change the leaving group. Table 17.4 shows what happens if we use the various methyl halides in reaction with NaOH. 

Transfer of organic groups from tin to carbon electrophiles, e.g. alkyl halides and acyl hahdes, can occur in the presence of a transition metal (e.g. Pd) catalyst (equation 40). Reactivity sequences for elecfrophihc carbon-tin bond cleavages are generally allyl > phenyl > benzyl > vinyl > methyl > higher alkyl. The precise sequence is somewhat dependent on the solvent and electrophile. 

Position C-2 of an imidazole is usually electrophilic. However, a 1,3-disubstituted imidazolium cation can easily be deprotonated at C-2, thus converting the carbon atom into a nucleophilic centre (Scheme 78). Sodium hydride deprotonates 1,3-dimesitylimidazolium chloride quenching with an electrophile such as isobutyl chloroformate then formed imidazolium-2-carboester 328 in good yield <2005JA17624>. Dimethyl carbonate N-methylated 1-methyl-imidazole, then an electrophilic substitution at C-2 gave imidazolium-2-carboxylate 331 (Scheme 78) <2005JA17624>. 

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