Hydrocarboxylation of alcohols

As vinylaromatics, used as substrates in the synthetic routes toward 2-arylpropionic acids described in the previous chapters, are often obtained by the dehydration of the corresponding alcohols, direct carbonylation of 1-arylethanols provides a shorter access to ibuprofen or naproxen. However, in the presence of the PdCl2(PPh3)2 catalyst, the use of strongly addic medium is necessary to obtain ibuprofen from l-(4-isobutylphenyl)ethanol with good ( 98%) selectivity [55]. A significant improvement in catalytic activity (with turnover frequendes up to 850 h ) has been achieved by 

Chaudhari s group by the use of either the PdCl2(PPh3)2/TsOH/LiCl system [56] or catalyst 29 [36]. Some attempts were made to carry out hydrocarboxylation of l-(4-isobutylphenyl)ethanol with polymer-supported catalysts, too [5 7]. The most effective catalytic system consisting of Pd/C, PPh3, TsOH, and LiCl showed both excellent activity (with TOP up to 3375 h ) and selectivity toward ibuprofen ( 99.2%) [58]. 

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Table 61. Hydrocarboxylation of alcohols and diols via Koch synthesis route...

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