Electron-rich aromatic carboxylic

Su and coworkers established a Pd-catalyzed method for decarboxylative Mizoroki-Heck coupling, in which 1.2 equiv. of p-benzoquinone is used in place of the Ag(l) salt. This method met with some success only with electron-rich (hetero)aromatic carboxylic acids [33]. Subsequently, the same authors reported that the Pd catalyst itself can induce decarboxylative Mizoroki-Heck coupling of aromatic carboxylic acids when dioxygen is used as the terminal oxidant completely replacing the Ag salt [34]. Depending on the structure of the acids, two different Pd catalysts were required for the Mizoroki-Heck coupling to occur Pd(OAc)j worked efficiently for electron-rich aromatic carboxylic acids, while the Pd(OAc)2/SIPr system (SIPr l,3-bis(2,6-diisopropylphenyl), 5-dihydroiniidazol-2-ylidene) enabled the use of electron-deficient substituents (Scheme 22.24) [34]. 

Finally, electron rich aromatic rings can also act as nucleophiles towards arynes, e.g. 2-phenylanisole is the major product of Ag+-catalyzed decomposition of benzenediazonium carboxylate in anisole (equa-... 

Monotrifluoroacetylated diaminopyrazole was first reacted with the free Kemp s triacid to produce the imide, followed by N-Boc protection and amide-coupling with a m-substituted aniline derivative. Final Boc-deprotection occurred on the chromatography column leading directly to the new receptor modules. The recognition site X was chosen to be ethyl as a neutral reference, acetyl for polar side-chains, nitro for electron-rich aromatic residues and carboxylate for basic amino acids (Figure 2.4.4). 

In aromatic systems, oxazolines can have three different functions (Fig. 4). Firstly, they can be used as protecting groups for carboxylic acids. Secondly, they activate even electron-rich aromatic systems for nucleophilic substitution. Fluorine or alkoxy groups in the ortho position can be substituted by strong nucleophiles such as Grignard reagents. Thirdly, when biaryl compounds with axial chirality are synthesized in these reactions, oxazolines can induce the formation of only one atropisomer with excellent selectivity. These three qualities were all used in the synthesis of 20, a precursor of the natural product isochizandrine [10]. 

Reaction of electron-rich aromatic compounds with TTFA leads to intermolecular oxidative coupling to form the corresponding biaryls without aromatic thallation. The reaction proceeds through one-electron transfer from aromatic compounds to Tl(III) to give an aromatic radical cation which leads to biaryls (Schemes 9.52 and 9.53 [52]). Intramolecular aryl coupling also occurs (Schemes 9.54 [53] and 9.55 [54]) and, further, when the carboxylic acid moiety is present, intramolecular as well as intermolecular lactonization occurs (Schemes 9.56 [55] and 9.57 [56]). 

Acylation of electron-rich aromatics is reported to occur efficiently and very easily through mixed carboxylic-triflic anhydrides without any catalyst. The reaction can be applied to methoxy- and alkylarenes and thiophene, with acetic and benzoic acid, in a neat mixture, or in nitromethane (65%-98% yield) at room temperature or at 45°C. 

Shiinada et cd., in their screening of catalysts for the acylation of electron-rich aromatic compounds with carboxylic acids, found that In(OTf)3 at 20mol% is able to catalyze such a reaction at 250 °C, with yield of 66% fear the acylation of p-xylene (solvent) with heptanoic add. However, Eu(NTf)3 gave better yields and was their catalyst of choice [112]. 

This method works also for electron-rich aromatic and a,/8-unsaturated carboxylic acids and requires neither heavy metals nor strong oxidants. Among the various thiohy-droxamic esters investigated, A-hydroxypyridine-2-thione derivatives are exceptionally efficient. They are conveniently available by reaction of the respective acyl chloride with the sodium salt of A-hydroxypyridine-2-thione or by DCC-mediated coupling of the free acid. The Barton reaction gives the best yields of bromo derivatives the corresponding iodo derivatives are produced in much lower yields. Chlorine donors do... 

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