Aryl compounds heterocycles

A number of methods are available for generating aryl radicals. They have been reviewed recently as has the evidence that the processes result in the generation of free aryl radicals, Those methods which have been used for the arylation of heterocyclic compounds are described here, and their applications to the arylation of specific heterocycles are discussed and tabulated in Section II,C,D and E. 

Modifications of this method, such as the use of the more stable diazonium trifluoroacetates and the decomposition of benzenedia-zonium zincichloride with zinc dust, have been used as sources of aryl radicals, although not in the arylation of heterocyclic compounds. Pyridine, quinoline, and thiophene can be phenylated by treatment with benzenediazonium chloride and aluminum trichloride. ... 

Phenyl radicals can be generated by the thermal decomposition of lead tctrabcnzoate, phenyl iodosobenzoate, and diphenyliodonium hydroxide,- - and by the electrolysis of benzoic acid.- These methods have been employed in the arylation of aromatic compounds, including heterocycles. A method of promise which has not been applied to the arylation of heterocycles is the formation of aryl radicals by the photolysis of aromatic iodides at 2537... 

There has been relatively little work on the mechanism of arylation of heterocyclic compounds, but the arylation of homocyclic compounds has been studied in great detail. Those mechanistic aspects of the reactions with heterocycles which have been examined parallel closely the corresponding aspects of the reactions of homocycles, and there is... 

Free-radical arylation of heterocyclic compounds is a relatively inefficient process in which yields of particular products greater than 50% are rare. This is the inevitable result of the high reactivity and low selectivity of aryl radicals not only is it usual for the heterocyclic compound to be attacked at each of its available positions, but, as shown in preceding sections, other by-products are numerous. Nevertheless, the method often presents the only short route to a given compound and it has been widely applied. Preparative uses are grouped in this section under the heading of the heterocyclic system concerned. 

A number of other examples of intramolecular arylations in heterocyclic compounds have been described and reviewed. ... 

Quaternary ammonium salts are organically substituted nitrogen compounds in which the nitrogen atom is pentavalent. Four of the substituents are alkyl, aryl or heterocyclic radicals and the fifth is an anion (a cationic charge). This anion is mostly chloride. Therefore we call them benzalkonium chlorides. 

Table 9.1 13C chemical shifts of some common heterocyclic and fused aryl compounds. 

Palladium chemistry involving heterocycles has its unique characteristics stemming from the heterocycles inherently different structural and electronic properties in comparison to the corresponding carbocyclic aryl compounds. One example illustrating the striking difference in reactivity between a heteroarene and a carbocyclic arene is the heteroaryl Heck reaction (vide infra, see Section 1.4). We define a heteroaryl Heck reaction as an intermolecular or an intramolecular Heck reaction occurring onto a heteroaryl recipient. Intermolecular Heck reactions of carbocyclic arenes as the recipients are rare [12a-d], whereas heterocycles including thiophenes, furans, thiazoles, oxazoles, imidazoles, pyrroles and indoles, etc. are excellent substrates. For instance, the heteroaryl Heck reaction of 2-chloro-3,6-diethylpyrazine (1) and benzoxazole occurred at the C(2) position of benzoxazole to elaborate pyrazinylbenzoxazole 2 [12e]. 

Palladium chemistry of heterocycles has its idiosyncrasies stemming from their different structural properties from the corresponding carbocyclic aryl compounds. Even activated chloroheterocycles are sufficiently reactive to undergo Pd-catalyzed reactions. As a consequence of a and y activation of heteroaryl halides, Pd-catalyzed chemistry may take place regioselectively at the activated positions, a phenomenon rarely seen in carbocyclic aryl halides. In addition, another salient peculiarity in palladium chemistry of heterocycles is the so-called heteroaryl Heck reaction . For instance, while intermolecular palladium-catalyzed arylations of carbocyclic arenes are rare, palladium-catalyzed arylations of azoles and many other heterocycles readily take place. Therefore, the principal aim of this book is to highlight important palladium-mediated reactions of heterocycles with emphasis on the unique characteristics of individual heterocycles. 

Carbohydrate derivatives, in which one or more of the oxygen atoms bonded directly to the carbon skeleton have been replaced by sulfur, are termed thiosugars. The placement of the sulfur atom at the anomeric position constitutes a special case, because thioglycosides, alkyl, aryl and heterocyclic, occupy a very important place as versatile glycosyl donors in glycosidation methodology. Anomeric thiocarbonyl compounds, on the contrary, have been less explored, although their potential and scope is likely to be similar. 

The reactions of the 5-oxazolanes 14 with aryllead triacetates are examples of the typical arylation of heterocycles by which products 15 are formed. After hydrolysis and decarboxylation, heterocyclic compounds 15 are converted to the arylglycines 16 in yields of 81-93% (Equation (5)).33... 

These reactions do not require reoxidants since the organic compounds reoxidize die palladium(O) in the initial replacement step. Most results have been obtained with vinyl, aryl and heterocyclic iodides and bromides because of the easy and convenient availability of the required halides, and because this reaction was discovered for these reactants first. 

An enantioselective organocatalytic reductive amination has been achieved using Hantzsch ester for hydrogen transfer and compound (21) as catalyst. This mild and operationally simple fragment coupling has been accomplished with a wide range of ketones in combination with aryl and heterocyclic amines.359... 

The coupling of aryl- and alkenylzinc reagents with various halides has widespread use in the cross-coupling of aromatic rings [101]. The reactions of zinc derivatives of aromatic and heteroaromatic compounds with aryl and heterocyclic halides have wide synthetic applications [103,104],... 

Dialkyl, diaryl, alkyl aryl, and heterocyclic tellurium oxides are known. Most of these compounds are white solids that are soluble in sodium hydroxide. Diorgano tellurium oxides appear to be oxidized by atmospheric oxygen. Their exposure to air should be minimized5. The protonation constant of dimethyl tellurium oxide in water was found to be 6 (pKa)6,7, and of bis[4-methoxyphenyl] tellurium oxide in acetonitrile 14.9s. The barrier to inversion for dihydrogen tellurium oxide (H2Te = 0), the parent compound of diorgano tellurium oxides, was determined as 92.4 kJ/mol (22.0 kcal/mol) by extended Hiickel calculations9. 

Figure 9.21 Aryl substituted heterocyclic compounds as PDE4 inhibitors.

Base-catalyzed reaction between an aryl diazonium salt and an aromatic hydrocarbon (or aromatic heterocycle) to form a diaryl compound (or aryl-substituted heterocycle) involves radical coupling reaction, as shown in Scheme 2.49. 

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