Coupling Ullman

In a synthesis of decinine a phenol was protected as a methanesulfonate that was stable during an Ullman coupling reaction and during condensation, catalyzed by calcium hydroxide, of an amine with an aldehyde. Aryl methanesulfonates are cleaved by warm sodium hydroxide solution. " ... 

In general, imines are too reactive to be used to protect carbonyl groups. In a synthesis of juncusol, however, a bromo- and an iodocyclohexylimine of two identical aromatic aldehydes were coupled by an Ullman coupling reaction modi-fied by Ziegler. The imines were cleaved by acidic hydrolysis (aq. oxalic acid, THF, 20°, 1 h, 95% yield). Imines of aromatic aldehydes have also been prepared... 

The Ullman reaction has long been known as a method for the synthesis of aromatic ethers by the reaction of a phenol with an aromatic halide in the presence of a copper compound as a catalyst. It is a variation on the nucleophilic substitution reaction since a phenolic salt reacts with the halide. Nonactivated aromatic halides can be used in the synthesis of poly(arylene edier)s, dius providing a way of obtaining structures not available by the conventional nucleophilic route. The ease of halogen displacement was found to be the reverse of that observed for activated nucleophilic substitution reaction, that is, I > Br > Cl F. The polymerizations are conducted in benzophenone with a cuprous chloride-pyridine complex as a catalyst. Bromine compounds are the favored reactants.53,124 127 Poly(arylene ether)s have been prepared by Ullman coupling of bisphenols and... 

The reduction of transition metal halides with Li has been recently extended by Boudjouk and coworkers for Ullman coupling (benzyl halide to bibenzyl) by Cu or Ni, using a low intensity cleaning bath (5J.). Ultrasound dramatically decreased the time required for complete reduction of the metal halides ( 12 h without, <40 minutes with ultrasound). The subsequent reactivity of the Cu or Ni powders was also substantially enhanced by ultrasonic irradiation. This allowed significant increases in the yield of bibenzyl (especially for Ni) at lower temperatures, compared to simple stirring. 

Figure 1 Selected examples of the Ullman coupling in complex syntheses.

The formation and properties of octafluorodibenzothiophene (85) have been the subject of a series of papers by Chambers et al. Ullman coupling of bis(2-bromotetrafluorophenyl)sulfide gives 85 in quantitative yield [Eq. (6)]. An alternative route to 85 involves treating 2,2 -dihydrooctafluorobiphenyl with butyllithium and reacting the... 

The antidepressant agent tampramine (44-6) can be viewed as a distant analogue of imipramine that contains an extra benzene ring and two additional nitrogen atoms. The preparation of this compound starts by Ullman coupling of chloropyridine (44-1) with the aminobenzophenone (44-2) more frequently used for benzodiazepine syntheses. Reduction of the nitro group in the product (44-3) leads to a diamine (44-4) that readily cyclizes to form the pyridodiazepine (44-5). Alkylation of the anion from the treatment of this with sodium hydride with 3-chloro-1 -dimethylaminopropane affords tampramine (44-6) [44]. 

Previously, diphenaldehyde has been made by the Ullman coupling of o-iodobenzaldehyde,6 6 by bromination of o/Z-bitolyl and hydrolysis of the resulting tetrabromo compound,7 and by lithium aluminum hydride reduction of the N-methylanilide of diphenic add.8 These methods involve more steps and give poorer yields than ozonolysis of phenanthrene. 

Diphenic acid has been prepared by the reduction of diazotized anthranilic acid with cuprous ion,5 Ullman coupling of potassium... 

Copper(l) triflate complexed with acetonitrile is effective for homogeneous Ullman coupling of aryl bromides T. Cohen and J. G. Tirpak, Tetrahedron Letters, 143 (1975) T. Cohen and I. Cristea, Am Soc, 98,748 (1976). 

Diphenic acid has been prepared by the reduction of diazotized anthranilic acid with cuprous ion,6 Ullman coupling of potassium o-bromobenzoate,6 and oxidation of phenanthrene or phen-anthrenequinone with various oxidizing agents.7 The latter methods have been reviewed recently.7 The ozonolysis method has also been carried out in solvents 8 that do not react with the zwitterion intermediate. ... 

The polymerization of a protected pyrrole has been reported based upon the Ullman coupling reaction [215,216,289]. As illustrated in Scheme 61, the 2,5-di-bromo-N-BOC-protected monomer was treated with CuCl followed by subsequent thermolysis to yield materials similar to those prepared in Scheme 60. Fractionation via HPLC made it possible to separate and characterize pyrrole oligomers up to n-20. 

This is an example of the Ullman coupling reaction. Other polyaromatic coupling reactions are provided (1). 

This instant invention represents an improvement in the Ullman coupling reaction. This investigation represents the first general method for coupling electron deficient phenols and unactivated aryl halides (1,2,3,4). The basis of the improvement lay in the high solubility of (CuOTf)2 benzene and cesium phenolate or copper phenolate in the reaction solvent, toluene. 

The mechanism of alkylation of AT-unsubstituted imidazoles and benzimidazole was discussed in CHEC(1984). Both CHEC(1984) and CHEC-II(1996) had extensive reviews on the topic, which are still relevant. A summary of improved Ullman coupling reactions is given in Table 9. 

Like the direct chemical change, the radical coupling mainly concerns fluorinated monomers. Ameduri and Boutevin [238] summarized the different studies concerning the modification of o ,rw-fluoropolymers in a recently published book. They showed, for instance, that extensive research [240] was carried out on the synthesis of diaromatic difunctional compounds linked to fluorinated chains according to the following Ullman coupling reaction ... 

An extremely simple one-pot synthesis of pyrazoles, pyrimidines, and isoxazoles has been realized by reacting enamino ketones, formed in situ with the appropriate bidentate nucleophile, under the action of microwaves [38]. Another approach to pyrazole from 4-alkoxy-l,l,l-trichloro-3-alken-2-ones and hydrazines, with toluene as solvent, is also possible under microwave conditions [39]. The Ullman coupling of (S)-[l-(3-bromophenyl)ethyl]ethylamine with N-H-containing heteroarenes such as pyrazole in N-methylpyrrolidone afforded the N-arylated compounds in high yields under microwave heating conditions at 198 °C [40]. 

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