Arenes with aryl halides

Scheme 39. Intramolecular Heck-type cyclization reactions of aryl halides with arenes a) Pd(OAc)2, DMF, K2C03, Bu4NBr, 140°C, 36 h [132b] b) Pd(OAc)2, DMF, K2C03, ttBu4NHS04,120°C, 51 h,X = Cl (3.2%),X = H (5.6%) [133]...

RXN68 Intramolecular Coupling of Aryl Halides with Arenes... 

The photoinduced reactions of aryl halides with the thiourea anion afford arene thiolate ions in DMSO. These species can be used without isolation for... 

Condensation of aryl halides with various active methylene compounds is readily promoted by catalytic action of palladium to give the corresponding arene derivatives containing a functionalized ethyl group [7]. Yamanaka et al. extended this chemistry to haloazoles including oxazoles, thiazoles and imidazoles [8]. Thus, in the presence of Pd(Ph3P)4,2-chlorooxazole was refluxed with phenylsulfonylacetonitrile and NaH to form 4,5-diphenyl-a-phenylsulfonyl-2-oxazoloacetonitrile, which existed predominantly as its enamine tautomer. In a similar fashion, 4-bromooxazole and 5-bromooxazole also were condensed with phenylsulfonylacetonitrile under the same conditions. 

Biaryls have also been prepared by coupling support-bound aryl halides with aryl-zinc compounds (Figure 5.20) or with aryl(fluoro)silanes [203]. As with Suzuki or Stille couplings, these reactions also require transition metal catalysis. An additional strategy for coupling arenes on solid phase is the oxidative dimerization of phenols (Figure 5.20). 

Halide displacement by thioanions such as thioalkoxides, thiocyanate and sulfite, can be readily carried out under PTC conditions in activated arenes. The reaction of nitro- and dinitro-aryl halides with thiophenol and NaOH in the presence of an ammonium or phosphonium salt catalyst proceeds readily in toluene at room temperature to give the phenyl aryl sulfides in nearly quantitative yield.189 Excellent yields of thiocyanoarenes were obtained from the reaction of the 2,4-dinitrohalobenzenes with KSCN in toluene at 90 C with a tetraalkyl onium salt PTC catalyst.190... 

The SrnI reactions are grouped according to the attacking element in the nucleophilic species, i.e. according to the new aryl-element bond being formed. These reactions are convenient one-step substitution reactions leading from aryl halides (or arenes with appropriate nucleofuges) to a variety of classes of aromatic compounds. 

The direct coupling of an aryl halide with an alkene to produce a phenylethene is known as the Heck reaction (Scheme 10.23). The mechanism involves coordination of the alkene to the palladium to form a k-complex 9 with which the arene ligand can react. A variety of substituents on the alkene is compatible with the reaction. 

Apart from their behaviour as ligands in metal catalyst systems, studies of the reactivity of phosphites towards a wide variety of other substrates have attracted attention. New aspects and applications of the classical Michaelis-Arbuzov reaction and its variants continue to appear. Evidence of the thermal disproportionation of methyltriaryloxyphosphonium halides formed in the reactions of triarylphosphites with alkyl halides, together with the formation of P-O-P intermediates, has been reported. The Michaelis-Arbuzov reaction has been used in the synthesis of phosphonate-based styrene-divinylbenzene resins and polyphosphonated chelation therapy ligands.Treatment of electron-rich benzylic alcohols dissolved in triethylphosphite with one equivalent of iodine affords a low-temperature one-pot route to the related benzylic phosphonates, compounds which are otherwise difficult to prepare. Upper-rim chloromethylated thiacalix[4]arenes have also been shown to undergo phosphonation on treatment with a phosphite ester in chloroform at room temperature. The nickel(II)-catalysed reaction of aryl halides with phosphite esters in high boiling solvents, e.g., diphenyl ether, (the Tavs reaction), has also... 

Blaser and Spencer used aroyl halides in place of aryl halides, with aroyl chlorides being of specific interest as ubiquitous, relatively cheap compounds ( Blaser reaction ) [24], This latter reaction is normally conducted in aromatic solvents phosphines are not used here as catalyst ligands since they fully inhibit the reaction. In the same way, benzoic acid anhydrides can be used as the aryl source in combination with PdCl2 and catalytic amounts of NaBr [79]. In this reaction, one of the arenes is used in the coupling reaction by elimination of CO, whereas the other benzoate serves as the base. The benzoic acid thus formed can easily be recycled into the anhydride. The use of aryl and vinyl triflates according to Cacchi [25] and Stille [26] extends the scope of the Heck coupling to carbonyl compounds phenol derivatives act via triflate functionalization as synthetic equivalents of the aryl halides. The arylation of cyclic alkenes [27], electron-rich vinyl ethers [28], and allylic alcohols [29] is accessible through Heck reactions. Allylic alcohols yield C-C-saturated carbonyl compounds (aldehydes) for mechanistic reasons (y9-H elimination), as exemplified in eq. (6). 

Even superheated (to 260 °C) or supercritical (to 400 °C) water was employed in the Heck reaction with several catalyst precursors and aryl halides with styrene. However, all conversions show large amounts of side products and the yields were in the 5-30% range, indicating radical intermediates and by-products from decomposition of the arene starting material [15]. 

Aryl-aryl coupling is an important synthetic reaction. Efficient aryl-aryl coupling is possible by Pd-catalyzed cross couplings of aryl halides with aryl metal (Mg, Zn, B, Sn, Si) compounds, and the methods have wide applications. On the other hand, a simple Pd-catalyzed arylation of arenes with aryl halides has been known. Although less attention has been paid, the importance of the reaction is increasing as more efficient methods of aryl-aryl bond formation become available. The arylation of arenes with aryl haUdes is treated in this section. 

Intermolecular arylation of carbocyclic arenes are rare. Exceptionally, phenols are easily arylated. As treated in Chapter 3.7.4, the aryl ether 48 is formed by reaction of aryl halides with hydroquinone monomethyl ether when bulky and electron-rich phosphines are used, which accelerate reductive elimination. Miura and co-workers found new completely different reactions of phenol with bromobenzene by using Pd(OAc)2, PPhs and CS2CO3 to give the unexpected pentaphenylated product 49 in 58% yield [lb, 15]. 

The use of Bu3SnH and AIBN has become commonplace in the synthesis of annulated arenes by the intramolecular aromatic substitution via aryl and heteroaryl radicals (see Chapter 13). Nevertheless, a simpler and more environmentally friendly protocol should be the direct generation of the o-aryl or heteroaryl radicals by UV-induced homo lytic cleavage of an aryl halide with subsequent intramolecular attack onto an arene in proximity. Accordingly, tricyclic [2,1-a] fused heterocycles were regioselectively formed in high yields from N-(2-arylethyl)-2-iodoimidazoles upon irradiation in acetonitrile (Scheme 14.18) [92]. 

In 2010, the groups of Charette and Lei independently reported an iron/diamine-catalyzed reaction of aryl iodides or bromides with a solvent amount of arene at 80-90°C (Eqs. 24 and 25) [60, 61]. A mixture of ortho-, meta-, and para-isomers was obtained when substituted arenes were used as the substrate, the ort/jo-isomer being the major product. The Charette group reported a KIE value of 1.04, while Lei group measured a KIE of 1.7. Based also on reaction inhibition by a radical scavenger, Charette suggested that radical processes are involved. Recent studies have revealed that cross-coupling of an aryl halide with an arene can proceed in the absence of a transition metal catalyst ([62] and references therein). 

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