Aromatic compounds heteroarenes

Under different conditions [PdfOAcj2, K2CO3, flu4NBr, NMP], the 1 3 coupling product 86 with 4-aryl-9,10-dihydrophenanthrene units was obtained. The product 86 was transformed into a variety of polycyclic aromatic compounds such as 87 and 88[83], The polycyclic heteroarene-annulated cyclopen-tadicnc 90 is prepared by the coupling of 3-iodopyridine and dicyclopentadiene (89), followed by retro-Diels Alder reaction on thermolysis[84]. 

In addition to the ligands above, considerable attention is given to more complex ligand systems [4,5] aromatic and heteroaromatic compounds (heteroarenes) (i.e., five- or six-member cyclic structures with delocalized 7i-bonds in the ring containing, besides carbon atoms, either N, P, As, O, S, Se, or Te compounds [6-8]), various chelate-forming compounds, such as macrocyclic crown-ethers, cryptands, porphyrins, and phthalocyanines. 

Thiation of aromatic compounds is utilized both for the preparation of aryl sulfides and for the generation of sulfur heteroarenes. The diaryl thioether motif is found in the structure of several approved pharmaceuticals, such as antihistamines. In a recent letter, Wu and He disclosed that Cu(I) catalysis is very efficient for the coupling of thiophenols with aryl iodides (Scheme 39) [ 108]. The procedure is very similiar to the diaryl ether synthesis under microwave irradiation reported by the same authors. 

Pyridine, the diazines, 1,3,5-triazine, 1,2,4,5-tetrazine, quinoline, isoquinoline, quinolizinium ion and the benzodiazines are HtiCKEL-aromatic systems (heteroarenes). 2//-Pyrane, 4//-pyrane and the corresponding benzo compounds, 1,4-dioxin, 1,4-dithiin and 1,4-oxathiin are not aromatic. However, the cations derived therefrom, like pyrylium and thiinium cations or dioxinium and dithiinium dications are aromatic the same is true for the corresponding benzo or dibenzo systems (e.g., benzopyrylium). Phosphinin is characterized by a specific heteroaromatic situation. 

The mechanism of these transformations is in agreement with that reported for the electrochemical process (Schemes 5 and 19). All these reactions result in the formation of products (yields are varied between 30 and 60%), and recover the starting aromatic compounds. The results are interesting enough to continue with a more extensive research on electrochemical reactions of these heteroarenes. 

In many cases electrochemistry proved to be a powerful tool to activate the SnAt reactions. The cathodic reduction in aromatic compounds, prior to their interaction with nucleophilic reagents, is a new essential step of the S Ar reactions. Moreover, a basic thermodynamic study explains (BDEs values of C-Nu vs. C-H), why F, OH, OR, and SR nucleophiles do not react with arenes or heteroarenes. 

C-H Arylation. Tris(l,l,l,3,3,3-hexafluoro-2-propyl)-phosphite (P[OCH(CF3)2]3) serves as a ligand in C-H activation reactions of aromatic compounds. For exartple, under the catalytic influence of RhCl(CO) P[OCH(CF3)2]3 2 and Ag2C03, the direct arylation of heteroarenes and arenes takes place with iodoarenes to afford a range of biaryls in good yields and with high selectivity. Thiophenes (eq 1), furans, pyrroles, indoles, and alkoxybenzenes are viable in this reaction. Instead of heteroarenes or arenes, allylsilanes also react with iodoarenes in the presence of RhCl(CO) P[OCH(CF3)2]3 2 catalyst to furnish the corresponding arylation product (eq 2) ... 

Heteroarene complexes, (C6R3H2E)2Ti (E = N, R=Buc E = P, R = Buc E = As, R = H, 20), can be prepared by metal-ligand vapor co-condensation of titanium with the corresponding arene (Scheme 4).15,16 Distinct 111 NMR resonances are observed for the aromatic protons at ambient temperature, suggesting restricted arene rotation. Variable-temperature NMR experiments provided barriers of 16 and 17kcalruol respectively, for the ring rotation. Reduction of either compound with potassium metal furnished the titanium(l) salts, KhC BuffTE )2Ti] (E = N, P 21). 

One class of transformations that illustrate the striking difference in reactivity between heteroarenes and carbocyclic arenes is the heteroaryl Heck reaction, in which an aryl or heteroaryl halide is coupled directly with a heteroaromatic compound to afford a biaryl product (formally a C—H bond functionalization process). Intermolecular Heck reactions involving the functionalization of aromatic carbocycles with aryVheteroaryl halides are rare [70], whereas heterocycles including thiophenes, furans, thiazoles, oxazoles, imidazoles. 

With this large group of heterocycles, ring strain is of little or no importance. Ring-opening reactions are, therefore, rarer than in three- and four-membered heterocycles. The crucial consideration is rather whether a compound can be regarded as a heteroarene or whether it has to be classified as a heterocycloalkane or heterocycloalkene (see p 2). Various aromaticity criteria apply to heteroarenes, and as a consequence, different opinions have been expressed on this matter [1]. As will be shown by means of examples of the various systems, the nature and number of heteroatoms are the critical factors. The parent compound of the five-membered heterocycles with one oxygen atom is furan. 

The methano-bridged aza[10]annulene 20 [9], a 10 r-analogue of pyridine, is a stable, yellow compound with a quinoline-like odour and a flattened perimeter (UV Amax 364 nm). The NMR data confirm the aromatic character of 20. The perimeter protons combine the features of a-substituted 1,6-methano[10]annulenes and quinoline (see p 318) the upheld shift of the bridge H-atoms (< ch2 = -0.40 / +0.65) is characteristic. It is caused by the shielding effect of the diatropic heteroarene system. The heteroannulene 20 is less basis (pX = 3.20) than pyridine (pX = 5.23) or quinoline pKa = 4.94). 

In general, electrochemical C-H functionalization of arenes and heteroarenes has been developed, as a new synthetic route to structurally modified aromatics. A number of transformations, such as cyanation, amination, C-arylation of ketones, alkylation, and phosphorylation have been performed by reacting arenes or heteroarenes with the cyanide ion, amines, ketones, RM and tetraalkylborate ions, and phosphorous compounds as nucleophiles, respectively. 

Arenes (benzenes, phenols, and anilines etc.) and heteroarenes (indoles, pyrroles, furans, thiophenes etc.) are very important commodity chemicals. Therefore, the addition of aromatic and heteroaromatic C—H bonds to unsaturated compounds would provide a clean and economic method for adding extra value to such compounds. However, the use of an iridium complex as the catalyst in this type of asymmetric C—C bond-forming reactions was not reported until 2000. 

A variety of methods for the catalytic direct arylation of aromatic and heteroaromatic compounds via the cleavage of C—H bonds has been developed during recent years. As complementary synthetic tools for conventional cross-couplings in the preparation of biaryls and arylated heteroarenes that require neither stoichiometric metallation nor halogenation, these reactions may be both useful and economical in a variety of situations. Consequently, it is highly likely that a major effort will be made in the near future to enhance the catalytic efficiency and regioselectivity of these reactions. 

Finally, sensitized photolysis of ethoxycarbonyl oximes of aromatic and heteroaromatic compounds, especially thiophene, yielded iminyl radicals (13BJOC1083). Iminyl radicals with suitably placed heteroarenes, such as benzothiophene shown below, underwent spiro-cyclization predominantly at low temperature, but thermodynamic control ensured that ortho products formed at higher temperatures. 

The gold-catalyzed reaction of alkynes with aromatic units has been extensively studied [105-107]. This reaction allows the synthesis of polycyclic aromatic and heteroaromatic systems via Friedel-Crafts-type processes. Although, the C-H activation of aryl compounds by gold(lll) has been known for more than 70 years, it is accepted that the Friedel-Crafts-type reaction proceeds via [Au(alkyne)] complexes and subsequent electrophilic aromatic substitution with the arenes or heteroarene compounds. 

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