Indoles carboxylic acids, decarboxylation, mechanisms

A semi-systematic study of the hydrolysis of ethyl indole-2-carboxylate in aqueous media at high temperature indicated that decarboxylation of indole-2-carboxylic acid proceeded by an arenium ion mechanism and was inhibited by base. Because base facilitated hydrolysis of the ester, it was possible to obtain either the acid or indole from the ester merely by manipulating the number of equivalents of base present. 

The intramolecular version of palladium-catalyzed decarboxylative cross-coupling reaction of aromatic carboxylic acids with organic halides also worked well. For example, 2-bromophenyl-tethered benzoic acids 116 underwent cyclization in the presence of Pd(OAc)2/PPh3 and K2CO3 in NMP to give 117 in high yields (Scheme 22.27) [51]. A mechanism that involved a sequence of oxidative addition, cyclization of carboxylate 118, decarboxylation of 119, and reductive elimination was proposed. Indole-2-carboxylic acid 121 was also applicable to this type of cyclization. 

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