Arenes, heterocycles

Regio- and stereo-selective synthesis of annulated arene heterocycles and carbocy-cles having a halo functionality is accomplished by Sm(OTf)3-catalysed alkylation of (S) arenes by a tethered alkene group using /V-halosuccinimide as a halogen source [e.g. 

Surprisingly not used in organic synthesis for decades, this methodology is now emerging with the synthesis of biaryls and of functionalized arenes, heterocyclic or not, as the goal.81... 

Overall, this coupling substrate showed the greatest flexibility in the coupling of arene heterocycles with a wide variety of 3-substituted (Ri-substituted) A - Pr-substituted a,P-unsaturated 2-acylimidazoles. The resulting acyl imidazolides could be converted in straightforward fashion to either aldehyde, ketone, acid, ester, or amide moieties using a one-pot two- or three-reaction sequence (not shown in scheme). ... 

Ruthenium(II) catalyst precursors and sometimes even simple RUCI3 derivatives are allowing easy activation of sp C-H bonds of functional arenes, heterocycles, alkenes, and further catalytic functionalization. These low-cost ruthenium (II) catalysts offer the advantages of their facihty of preparation, stability even often in the presence of water or as a solvent. The sp C-H bond activation with Ru (II) catalyst usually occurs at room temperature, via deprotonation of the C-H bond affording a metallacycle. However the further functionahzation of the (CH) carbon usually requires more energy. 

Many heterocyclic systems contain double bonds and are related to arenes The most important representatives of this class are described m Sections 11 22 and 11 23... 

Arene oxides of heterocycles such as pyridine have often been postulated as photoisomerization intermediates (81H(15)1569,72JOC3592) but to date they have not been isolated or extensively studied. 

Cavity design using calix[n]arenes with heterocyclic fragments 97CRV1713. 

Noncovalent synthesis of organic nanostmctures, hydrogen-bonded ensembles including heterocyclic analogs of calix[4]arenes 98PAC1459. 

Numerous reactions have been described in which the oxygen of the oxepin system is removed to give benzene derivatives. The formation of the aromatic products can be rationalized by an arene oxide as intermediate. A suitable reagent for the elimination of an oxygen atom from this heterocycle is triphenylphosphane, e.g. formation of l,24 2a,12 and 2b.1,9... 

Thiazoles are important heterocycles and continue to be interesting synthetic targets because several classes of annulated thiazoles and thiazolyl (hetero)arenes display a diverse array of biological activities. 

As was suggested in the preceding discussion, most of the arene complexes isolated by metal-atom techniques are benzene derivatives. However, heterocyclic ligands are also known to act as 5- or 6-electron donors in transition-metal 7r-complexes (79), and it has proved possible to isolate heterocyclic complexes via the metal-atom route. Bis(2,6-di-methylpyridine)Cr(O) was prepared by cocondensation of Cr atoms with the ligand at 77 K (79). The red-brown product was isolated in only 2% yield the stoichiometry was confirmed by mass spectrometry, and the structure determined by X-ray crystal-structure analysis, which supported a sandwich formulation. 

Trifluoromethyl groups that are bound to sp2 carbons of alkenes, arenes, or heterocyclic compounds are slightly deshielded compared to the saturated counterparts, but the influence is relatively small (Scheme 5.32). 

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]. 

One active field of research involving the Heck reaction is asymmetric Heck reactions (AHR). The objective is to achieve enantiomerically-enriched Heck products from racemic substrates using a catalytic amount of chiral ligands, making the process more practical and economical Although intermolecular Heck reactions that occurred onto carbocyclic arenes are rare, they readily take place onto many heterocycles including thiophenes, furans, thiazoles, oxazoles,... 

In conclusion, the Pd chemistry of pyrimidines has its own characteristics when compared to carbocyclic arenes and other nitrogen-containing heterocycles such as pyridine and imidazole. One salient feature of halopyrimidines is that the C(4) and C(6) positions are more activated than C(2). As a result, 2-, 4- and 6-chloropyrimidines are viable substrates for Pd-catalyzed reactions and 4- and 6-chloropyrimidines react more readily than 2-chloropyrimidines. For the Sonogashira reaction, though, there is little difference in the reactivity among 2-, 4- and 5-positions of substituted halopyrimidines. Not only is the Sonogashira reaction a reliable method... 

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. 

Another isomerization reaction of arene oxides is equilibrium with oxe-pins [5], Here, the fused six-membered carbocycle and three-membered oxirane merge to form a seven-membered heterocycle, as shown in Fig. 10.2. An extensive computational and experimental study involving 75 epoxides of monocyclic, bicyclic, and polycyclic aromatic hydrocarbons has revealed much information on the structural factors that influence the reaction rate and position of equilibrium [11], Thus, some compounds were stable as oxepins (e.g., naphthalene 2,3-oxide), while others exhibited a balanced equilibrium... 

The photolysis of donor-acceptor systems shows a reaction pattern of unique synthetic value. Direct irradiation of the donor-acceptor pairs, such as arene-amine, leads by intramolecular electron transfer, to amine radical cations and arene radical anions. The generated radical cation and radical anion intermediates undergo cyclization reactions providing efficient synthetic routes to N-heterocycles with a variety of ring sizes. 

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