Arylacetic acid derivatives, dimethyl

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... 

In an industrial asymmetric synthesis en route to the antiinflammatory agent naproxen, the dimethyl L-tartrate acetals of ethyl aryl ketones are brominated in high yield and selectivity to give the corresponding a-bromo derivatives. Subsequent stereospecific Ag -promoted 1,2-aryl migration provides the 2-alkyl-2-arylacetic acid after hydrolysis of the tartrate auxiliary, which is recovered (e.g. eq 4). 

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