Selective monomethylation arylacetates

Among the different synthetic procedures available for the preparation of hydratropic acids (e.g., indirect methylation of arylacetic acids,4 asymmetric hydroformylation of styrenes,5 rearrangements of a-bromoalkyl aryl ketals,6 etc.), direct methylation of arylacetic acid derivatives seems the most attractive from both economical and synthetic aspects the reagents are easily accessible and a one-pot reaction is involved. Nevertheless, this procedure is seldom used since the yields of the monomethyl derivatives are severely limited by the low selectivity of the reaction. Sizeable amounts of dimethylated by-products form.2 Even under phase-transfer catalysis conditions, high selectivity in monomethylation is elusive.7-8... 

The unusually high selectivity observed in the monomethylation of methyl aryloxyacetates and aryloxyacetonitriles may be explained by the mechanism previously described for the reaction of DMC with methyl arylacetates and arylacetonitriles (6) in which ArCH(COOCH3)X and ArC(CH3)(COOCH3)X are the key intermediates. It is likely that this reaction proceeds through the formation of methyl-carboxymethyl intermediates, ArOC(CH3)(COOCH3)X, as these derivatives were actually detected by GC/MS during the course of the reaction. In this case, the attack on the acyl carbon, which produce the possible intermediate PhC(COOCH3)2X, does not affect selectivity, because it is an equilibrium reaction. 

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