Decarboxylation arylation

Scheme 48 Proposed mechanism for the C2- and C3-decarboxylative arylation of indoles.

A novel copper-catalyzed decarboxylative arylation of a variety of benzoxazoles with 2-nitrocarboxyhc acids (218) was reported to be most effective with electron-rich benzoxazoles by Hoover and coworkers (2015CC15059). Moreover, the presence of the ortho-nitro group was found to be essential for coupling, suggesting that this group plays a role in faciH-tating the decarboxylation step. 

Interestingly, N-phenyl-2-thiophenecarboxamides undergo 2,3,5-triarylation accompanied by a formal decarbamoylation upon treatment with excess bromo-benzenes (Equation 10.50) [74]. The reaction involves an initial coordination-assisted 3-arylation and successive decarbamoylation which is promoted by a Pd(II) species and the stoichiometric base. A related decarboxylative arylation of 2-thiophenecarboxylic acids at the ipso-position has been reported (Equation 10.51) [75]. The introduction of an electron-withdrawing group at the 3-position of thiophene makes the 4-arylation possible, while the reaction at 2- and 5-positions precedes. Thus, the reaction of 3-cyanothiophene affords the corresponding 2,4,5-triarylated products (Equation 10.52) [74]. Whilst the mechanism for the 4-... 

Scheme 3.4 Synthesis of diarylindoles by palladium-catalyzed direct and decarboxylative arylations of carboxyindoles, as described by Miura and coworkers [14].

In 2013, Jafarpour and coworkers [22] reported a versatile, regioselective, and step-economical decarboxylative arylation of coumarin-3-carboxylic acids via a ligand-free palladium-catalytic system (Scheme 3.10). This protocol was compatible with a wide variety of electron-donating and electron-withdrawing substituents, and allowed the construction of several biologically important ic-electron-extended coumarins. 

Scheme 3.9 Decarboxylative arylation of an imidazo[1,2-a]pyridine-3-carboxylic acid and an 3-(4-fluorophenyl)-5-methylisoxazole-4-carboxylic acid with aryl halides, as described by Lee and coworkers [21].

In 2013, Satoh, Miura, and coworkers [39] reported the palladium-catalyzed decarboxylative ary-lation of readily available 3-benzoylacrylic acids with arylboronic acids in the presence of a copper salt oxidant, affording chalcone derivatives (Scheme 3.22). The decarboxylative arylation could also be achieved using aryl halides as an alternative aryl source (Scheme 3.22). 

Scheme 3.22 Palladium-catalyzed decarboxylative arylation of benzoylacrylic acids for the synthesis of...

Scheme 3.25 Ruthenium catalyzed decarboxylative arylation at sp carbon centers in pyrrolidine and piperidine heterocydes, as described by Sames and coworkers [42].

The direct arylation of less electron-rich azoles via cleavage of the relatively acidic C-H bond of their C2-position with ortho-substituted benzoic acids was achieved (Scheme 4.14) [18]. Similarly, the decarboxylative arylation procedure on C-H bond was successfully applied to electron-deficient polyfluoroarenes... 

In 2006, Forgione, Bilodeau, and coworkers succeeded in conducting the decarboxylative arylation of heteroarenecarboxylic acids such as pyrrole- and... 

The decarboxylative arylation of thiazole- and oxazole-5-carboxylic acids with aryl halides occurs in the presence of a Pd/Ag system (Scheme 4.46) [51]. The azole-azole coupling also proceeds through decarboxylation and C-H bond cleavage (Scheme 4.47) [52]. 

The decarboxylative arylation of propiolic acids with arylboronic acids can be conducted under oxidative conditions (Scheme 4.64) [65]. 

The decarboxylative arylation of potassium oxalate monoesters also occurs to give the corresponding aromatic esters (Scheme 4.68) [70]. The decarboxylative oxidative coupling of a-keto carboxylic acids with aryltrifluoroborates takes place in the presence of a palladium catalyst together with (NH4)2S20g as oxidant (Scheme 4.69) [71]. a-lmino carboxylates also undergo decarboxylative... 

Ge and coworkers reported the decarboxylative arylations of a-keto carboxylic acids with acetanilides [74] and 2-phenylpyridines [75] via C-H bond cleavage at their 2 and 2 -positions, respectively (Schemes 4.72 and 4.73). The procedure was successfully applied to the reactions of cyclic enamides (Scheme 4.74) [76]. 

The decarboxylative coupling of potassium 2-(2-pyridyl)acetates with aryl halides can be carried out efficiently under palladium catalysis (Scheme 4.77) [80]. Based on DFT calculations, it was proposed that coordination of the pyridyl nitrogen to Pd is crucial to reduce the energy barrier of the rate-limiting decarboxylation step. a-Cyanoacetates also undergo similar decarboxylative arylation to produce a-aryl nitriles (Scheme 4.78) [81]. From the same combination of substrates, a,a-diaryl nitriles can also be selectively prepared by double arylation (Scheme 4.79) [82]. 

The decarboxylative arylation of 2,5-cyclohexadiene-l-carboxylic acids occurs under palladium catalysis (Scheme 4.82) [86]. 

It must be noted that when the saturated cyclic amine was protected in 2-position by an ester group (proline derivative), sp C-H bond activation did not operate at C5 but a decarboxylative arylation took place in the absence of pinacolone leading to monoarylated pyrroline products (Scheme 19) [13]. 

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