Carboxylic acids decarboxylative coupling, quinoline

In order to evaluate what caused the limitation to ort/io-substimted carboxylic acids, we investigated the decarboxylation step separately firom die cross-coupling step. In the presence of only the copper(I) phenanthroline/quinoline decarboxylation catalyst (15 mol%), a wide range of aromatic, heteroaromatic, and vinylic carboxylates protodecarboxylated to the corresponding hydrocarbons rai heating to 160°C (Scheme 12). However, added halide ions, as would inevitably be released in a decarboxylative cross-coupling (Scheme 6), prevented the decarboxylation for aU non-orf/io-substituted or not otherwise activated aromatic carboxylic acids. 

Goossen and coworkers reported the decarboxylative coupling of a-keto carboxylic acids with aryl bromides (Scheme 4.67) [69]. Thus, treatment of potassium 2-oxo-2-phenylacetates with 4-bromotoluene in the presence of 1 mol% of palladium 1,1,1,5,5,5-hexafluoroacetylacetonate, 2mol% of P(o-tolyl)3, 15mol% of CuBr, 15mol% of 1,10-phenanthroline in NMP/quinoline at 170 C gives the corresponding benzophenones. 

With the preliminary results in hand, it was crucial that the C2 group on the indole could be readily removed. The C2 carboxylic acid derivatives of coupling products were initially employed toward this endeavor (Scheme 4). There are relatively few decarboxylation methods on indole acids reported in the literature, most of which utilize harsh reaction conditions. Nevertheless, Jagan tested several of the reported methods, including the use of copper chromite in quinoline at 215 °C, copper(I)oxide in DMA at 200 °C, and substoichiometric amounts of indole acid copper salts at 200 Much to his dismay, most of these reactions led to decomposition. Moreover, adjusting temperature or switching to microwave heating failed to provide the desired decarboxylation. 

In general, the PET decarboxylation of carboxylic acids exhibits low product selectivity, due to the subsequent radical coupling in solution however, the PET reaction between potassium propionate and the methyl ester of N-methyltrimellitic acid imide is highly regioselective to the para-addition product. This contrasts with other intramolecular and intermolecular PET reactions of quinolinic acid imides, which do not show a high degree of regioselectivity (Scheme S)." ... 

The Doebner reaction is a three component coupling of an aniline (1), pyruvic acid (2), and an aldehyde (3) to provide a 4-carboxyl quinoline (4). That product can be decarboxylated to furnish quinoline 5. 

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