Arenes and Heteroarenes

In this chapter we discuss only the physical structure of arene- and heteroarene-diazonium ions and salts. The chemical reactions of diazonium ions and the chemical structures of the products will be the subject of later chapters. 

Boyd DR, ND Sharma, R Boyle, RAS McMordie, J Chuna, H Dalton (1992) A h NMR method for the determination of enantiomeric excess and absolute configuration of ciT-dihydrodiol metabolites of polycyclic arenes and heteroarenes. Tetrahedron Lett 33 1241-1244. 

The reactions of heteroaromatic compounds such as furans, pyrroles, and indoles with alkynoates proceed under very mild conditions (in acetic acid or even in neutral solvents such as CH2C12 at room temperature). For example, the reaction of pyrrole with ethyl phenylpropiolate gives the 2-alkenylated pyrrole (Equation (44)).47c This reaction is applied to the direct synthesis of a /3-alkenylpyrrole, the pyrrole fragment of haemin (Equation (45)).47d The present reaction provides a very convenient method for functionalization of arenes and heteroarenes. 

The direct borylation of arenes was catalyzed by iridium complexes [61-63]. Iridium complex generated from [lrCl(cod)]2 and 2,2 -bipyridine (bpy) showed the high catalytic activity of the reaction of bis (pinaco la to) diboron (B2Pin2) 138 with benzene 139 to afford phenylborane 140 (Equation 10.36) [61]. Various arenes and heteroarenes are allowed to react with B2Pin2 and pinacolborane (HBpin) in the presence of [lrCl(cod)]2/bipyridne or [lr(OMe)(cod)]2/bipyridine to produce corresponding aryl- and heteroarylboron compounds [62]. The reaction is considered to proceed via the formation of a tris(boryl)iridium(lll) species and its oxidative addition to an aromahc C—H bond. 

The synthesis of 1,4-dithiines from arenes and heteroarenes has been known for more than 100 years. The reaction of quinoline and sulfur monochloride gave dithiodiquinoline 152 (R = R = H) (1896JPR340). The structure of such compounds has been correctly identified only recently (1976PJC785, 1997JCR(S)435 Scheme 80). 

Beside the Friedel-Crafts-type alkylation of arenes, the direct functionalization of 2,4-pentanediones is of great interest in Lewis acid catalysis. Although Pd-catalyzed Tsuji-Trost type allylations of 1,3-diketones are known, direct benzylation procedures catalyzed by Lewis acids are less explored [40-43]. Based on the previously described Friedel-Crafts alkylation of arenes and heteroarenes, the Rueping group developed a Bi(OTf)3-catalyzed benzylation of 2,4-pentanediones. Alcohols such as benzyl, allyl or cinnamyl alcohols were used as the electrophilic component to yield important 2-alkylated 1,3-dicarbonyl compounds. Initially, different Bi(III) salts were screened. In contrast... 

Figure 4.1. Lithiation of polystyrene-bound arenes and heteroarenes [1,8-10],...

The alkylation reaction is limited to nitro-substituted arenes and heteroarenes and is highly chemoselec-tive nucleophilic displacement of activated halogens, including fluorine, was not observed. The regio-selectivity is determined by the bulkiness of the silicon reagent. With unhindered silyl derivatives a strong preference for ortho addition was observed, as in the example of equation (6). With bulkier reagents attack took place exclusively at the para position (Scheme 1). The success of this reaction, which could not be reproduced with alkali enolates, was attributed at least in part to the essentially nonbasic reaction conditions under which side processes due to base-induced reactions of nitroarenes can be effectively eliminated.12... 

One of the most common examples of an electrophilic aromatic substitution is Friedel-Crafts alkylation [40], These days, many important industrial processes are based on this type of Friedel-Crafts-chemistry [41]. The manufacture of high-octane gasoline, ethylbenzene, synthetic rubber, plastics and detergent alkylates are examples. Moreover, the Friedel-Crafts alkylation is among the most fundamental and convenient processes for C—C bond formation on arenes, especially for the synthesis of fine chemicals and agrochemicals containing functionalized arenes and heteroarenes. 

Iron salts (e.g. FeCls) have been identified as new catalysts for intramolecular hydroamination. A number of olefinic tosylamides underwent the reaction at 80 °C to form the corresponding the N-tosylpyrrolidine derivatives in good yield.63 The same salt can also catalyse Markovnikov addition of electron-rich arenes and heteroarenes to styrenes, giving rise to 1,1-diarylalkanes at 80 °C.64... 

Homolytic aromatic substitution is a valuable method for the substitution of arenes and heteroarenes, and has been reviewed recently by Studer and Bossart [ 16]. Both intramolecular [16] and intermolecular reactions [17] with arenes have become increasingly useful in synthesis. The intramolecular variant has received more attention with many elegant applications reported [18]. 

Scheme3.20. Oxidation potentials (vs Ag/Ag+) and gas-phase ionization potentials (in parentheses) of some arenes and heteroarenes and triplet oxygen [56, 57, 70, 74, 77-79], Ref[56] 1.83 V.

Arenes and heteroarenes which are particularly easy to metalate are tricarbo-nyl( 76-arene)chromium complexes [380, 381], ferrocenes [13, 382, 383], thiophenes [157, 158, 181, 370, 384], furans [370, 385], and most azoles [386-389]. Meta-lated oxazoles, indoles, or furans can, however, be unstable and undergo ring-opening reactions [179, 181, 388]. Pyridines and other six-membered, nitrogen-containing heterocycles can also be lithiated [59, 370, 390-398] or magnesiated [399], but because nucleophilic organometallic compounds readily add to electron-deficient heteroarenes, dimerization can occur, and alkylations of such metalated heteroarenes often require careful optimization of the reaction conditions [368, 400, 401] (Schemes 5.42 and 5.69). 

A simple chiral silane [(13), 2 1 mixture of diastereoisomers] mediates the enan-tioselective reaction of electron-rich arenes and heteroarenes with the benzoylhydra-zone of isopropyl glyoxylate under optimized conditions, leading to a useful synthesis... 

In contrast to the observed reactivity of phenoxide and aryl alkoxide ions, arene and heteroarene thiolate ions typically couple with aryl radical to generate C—S bonds. The only exception to this regioselective reaction is the addition of 1-naphthalene thiolate ion to p-anisyl radical to render both C- and S-substitutions in 14% and 65% yields, respectively, while with 1-naphthyl radical, 95% of C—S coupling is obtained. In general, PhS- ions react with Arl in liquid ammonia under photostimulation to afford good yields of ArSPh or heteroaryl-SAr (70-100%). Substitution of the less-reactive ArBr can be achieved under photochemical initiation in DMF, MeCN, or DM SO [1],... 

It is generally admitted that skeletal transformations of hydrocarbons are catalyzed by protonic sites only. Indeed good correlations were obtained between the concentration of Bronsted acid sites and the rate of various reactions, e g. cumene dealkylation, xylene isomerization, toluene and ethylbenzene disproportionation and n-hexane cracking10 12 On the other hand, it was never demonstrated that isolated Lewis acid sites could be active for these reactions. However, it is well known that Lewis acid sites located in the vicinity of protonic sites can increase the strength (hence the activity) of these latter sites, this effect being comparable to the one observed in the formation of superacid solutions. Protonic sites are also active for non skeletal transformations of hydrocarbons e g. cis trans and double bond shift isomerization of alkenes and for many transformations of functional compounds e.g. rearrangement of functionalized saturated systems, of arenes, electrophilic substitution of arenes and heteroarenes (alkylation, acylation, nitration, etc ), hydration and dehydration etc. However, many of these transformations are more complex with simultaneously reactions on the acid and on the base sites of the solid... 

The Au-catalysed [3,3] sigmatropic rearrangement of propargyl propynoates 29 leads to 5-vinylpyran-2-ones probably by way of a cationic intermediate 30 (Scheme 23). This oxocarbenium ion can be intercepted by electron-rich arenes and heteroarenes with attack occurring at the vinylic double bond leading to more complex pyranones <07AG(E)8250>. 

A highly regioselective borylation of arenes and heteroarenes (such as benzo[ ]furan 82) was achieved by the iridium-catalyzed C-H activation reaction, as shown in Equation (94) <2003CC2924>. 

Mechanistically Related Reactions of Arenes and Heteroarenes with Alkynes 18... 

MECHANISTICALLY RELATED REACTIONS OF ARENES AND HETEROARENES WITH ALKYNES... 

The scope of this reaction is limited to electron-rich arenes and heteroarenes such as thiophenes, pyrroles, furans, indoles, and alkoxybenzenes as nucleophilic partners, corresponding to a Mayr ir-nucleophilicily parameter N>-1 [75-78], Electron-neutral to electron-deficient iodo(hetero)arenes are suitable electrophilic partners. Aryl halides or pseudohalides that are less reactive towards oxidative addition (Br, Cl, OTf) are not sufficiently reactive partners in this reaction. The reactivity of sterically hindered and/or ortho substituted iodoarenes has not been demonstrated. However biaryls bearing one ortho substituent of relatively small steric demand (e.g., from methoxybenzene or /V-mcthylindole) have been prepared. 

Owing to its Lewis acidity, zinc complex 106 lends itself to schemes for alkylation of electron-rich arenes and heteroarenes such as pyrroles by way of conjugate addition. An even more valuable method is the 3-component condensation that unites indole with a nitroalkene and an aldehyde. Three contiguous stereocenters are established in a controlled manner and in an absolute sense by conducting the reaction in the presence of CuOTf, 126, and hexafluoroisopropanol. ... 

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