CHAcidic Compounds

The methylation of arylacetic acid derivatives is chosen as a model reaction for the mechanistic discussion. Experimental evidence of DMC-mediated alkylation of ArCH2X (X = CN, CO2Me) with DMC supports the hypothesis that the reaction does not proceed through a SN2 displacement of the ArCH(_)X nucleophile on DMC (BAl2 mechanism).19a Rather, the selectivity arises from consecutive reactions involving two intermediate species observed during the reaction: ArCH(CO2Me)X (3) and ArC(CH3)(CO2Me)X (4).

As an example, Figure 4.4 depicts the outcome of the mono-C-methylation of o-tolylacetonitrile with DMC: the two compounds o-CH3C6H4CH(CO2Me)CN and o-CH3C6H4C(Me)(CO2Me)CN (shown as c and d, respetively) are the reaction intermediates. In general, however, intermediates 3 are very reactive moieties (as confirmed by the kinetic investigation of the reaction, see later), whose identification in the reaction mixture very often fails. In the case of Figure 4.4, it is probably the steric hindrance of an o-Me substituent that affects the reactivity of compound c. The pattern for the reaction mechanism is outlined in Scheme 4.10.

Initially, the carbanion [ArCH(_)X] undergoes a methoxycarbonylation reaction by attacking the acyl carbon of DMC (BAc2 mechanism). The resulting intermediate [ArCH(CO2Me)X, (3)] reacts through its anion [ArC(_)(CO2Me)X, (3")] with the alkyl carbon of DMC to yield the corresponding methyl derivative [ArC(CH3)(CO2Me)X, (4); BAl2 mechanism]. Finally, compound 4 is subjected to a demethoxycarbonylation reaction to produce the final product [ArCH(CH3)X].

This mechanism also applies to other CH2-active compounds such as derivatives of aroxyacetic acid and benzylic sulfones, whose methylation reactions with

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