Homocoupling carboxylic acids

Diaryl ketones.2 In the presence of this complex (1 equivalent) S-(2-pyridyl) aryl thioates (1 equivalent), prepared from aryl carboxylic acids, undergo reductive homocoupling to diaryl ketones (equation I). 

Polar substituents can be handled without protection because nonpolar radicals are involved as reactive intermediates. This saves steps for protection and deprotection that are necessary when substrates with such substituents are submitted to reactions where strong bases, nucleophiles and electrophiles are involved. Together with the availability of a wide variety of carboxylic acids, this method of homocoupling is a unique and attractive method for the construction of symmetrical compounds. A great number of homocoupling reactions have been tabulated in refs. [2, 25, 26]. Table 2 and molecular structures 8-17 show some selected examples. 

In a handful of cases, two CCXIH groups have been activated for the synthesis of biaryls. Larrosa and coworkers reported for the first time the decarboxylative homocoupling of aromatic acids mediated by Pd and Ag [62a]. The reaction makes use of Pd(TFA)j as a catalyst and Ag CO as an additive to afford the desired biaryls in 76-95% yields. The only by-products observed were due to the proto-decarboxylation of the aryl carboxylic acid. Both metals are essential for the reaction, and the role of the Ag salt is not only as the terminal oxidant but also as a mediator of the decarboxylation process. The method is subject to some limitations on the substituents on the benzoic acids. Thus, m- and p-nitrobenzoic acids as well as benzoic acids ortho substituted with F, Br, or MeO failed to give decarboxylative homocoupling products. In all cases, protodecarboxylations to the corresponding arenes were the main products observed. The same problem was reported in the protocol developed by Deng and coworkers, where the best results were obtained with PdCl and PPhj in the presence of Ag COj [62b]. 

Scheme 3.14 Decarboxylative homocoupling of (hetero)aromatic carboxylic acids, as described by Larrosa...

Silver(I) carbonate is responsible for generating an aryl silver species, which can subsequently undergo transmetalation with Pd. To prevent protodecarboxylation and decarboxylative homocoupling, tricyclohexylphosphine was required to accelerate transmetalation and reductive elimination. Electron-rich, electron-deficient, and heterocyclic benzoic acids were compatible coupling partners and a wide range of functional groups were tolerated for both thiophene and carboxylic acid moieties. Additional heterocycles such as benzothiophenes and 2-methylfuran could also be arylated. 

Silver(I) carbonate functioned as an cooxidant with TEMPO. Tricyclohexylphosphine was employed to suppress homocoupling between heteroarenes. Substituted thiophenes, furans, and indoles could be selectively olefinated (C5-alkenylation for thiophenes and furans, C3-alkenylation for indoles, E/Z > 99 1). Unsubstituted thiophenes produced poor yields (24%) however, formyl, acetyl, and ketyl substituents were well tolerated. For electron-deficient substrates, tricyclohexylphosphine was reduced to 10 mol % to achieve good conversions. A variety of ketones could be employed using 2-methyl thiophene as a coupling partner. A related methodology employing saturated ketones and heterocyclic carboxylic acids via a Pd-catalyzed decarboxylative process was also reported (eq 44). ... 

Carboxylates with different non-racemic chiral auxiliaries have been anodically de-carboxylated to explore the face-selective hetero- and homocoupling of the intermediate radicals. 2-Substituted malonamides were subjected to heterocoupling with different coacids. In the acids 30a-c, (2/ ,5.R)-2,5-dimethylpyrrolidine served as chiral amido group. 

Catalytic carbon-carbon bond formation has been achieved using boron derivatives but requires the right choice of oxidant, otherwise homocoupling of the added organometallic (Section 2.10) may occur. Ben-zoquinone (BQ) has been found to be effective, combined with direction of CH activation by pyridine (Scheme 3.61), ° by carboxylates (Scheme 3.62) and by hydroxamic acids. Air has been used as the... 

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