Arenes nucleophilic addition reactions

Synthetically useful reactions of (arene)Mn(CO)3+ complexes with such nucleophiles as methoxide, benzenethiolate, azide, various amines, and anilines are also noteworthy. These complexes have also been extensively studied with regard to nucleophilic addition reactions resulting in thermally stable cyclohexadienyl complexes [2]. 

In general, nucleophilic addition reactions of arene oxides with nonpolarizable oxygen and nitrogen nucleophiles are very slow. Thus both NH3 and NHj nucleophiles failed to add to benzene oxides under a range of conditions. Amine nucleophiles have, however, been found to react very slowly with benzene oxide. 

Most osmium complexes of phenols [26,44], anilines [24,45], and anisoles [23, 46,47] undergo electrophilic addition with a high regiochemical preference for para addition. While electrophilic additions to phenol complexes are typically carried out in the presence of an amine base catalyst, the other two classes generally require a mild Lewis or Bronsted acid to promote the reaction. The primary advantage of the less activated arenes is that the 4H-arenium species resulting from electrophilic addition are more reactive toward nucleophilic addition reactions (see below). 

Fig. 2. Reactions of arene oxides. Spontaneous aromatization into phenols and nucleophilic addition reactions by amines and thiols...

MO calculations suggest that, in nucleophilic addition reactions of substituted benchrotrenes [( -PhX)Cr(CO)3] (see Vol. 9, ref. 412), the preferred orientation of addition is influenced more by the conformation of the Cr(CO)a residue than by the electronic character of the substituent X. Whereas lithiation (with BuLi-TMED) of 3-methoxybenzyl alcohol occurs very predominantly at the 2-position of the arene ring, similar treatment of the corresponding n-Cr(CO)3 complex gives a mixture of the 2- and 4-lithio derivatives in the ratio 23 77, respectively these products were characterized by isolation of carboxylic acid derivatives following carbonation (COg) and metal decomplexation hv 0. Experimental details for the preparation of [(iy-PhX)Cr(CO)3] (X=I and SiMes) from [( -PhLi)Cr(CO)3] have been reported. This lithio derivative has also been used to prepare the carbene complexes [(OC)3Cr(i7-Ph)C(OEt)M(CO)5] (M=Cr, Mo, and W), which react with BX, (X=C1 and Br) to give the carbyne products [(OC)3Cr( Ph)C=M(CO)4X] (M=Cr and W only). ... 

The first use of chiral oxazolines as activating groups for nucleophilic additions to arenes was described by Meyers in 1984. " Reaction of naphthyloxazoline 3 with phenyllithium followed by alkylation of the resulting anion with iodomethane afforded dihydronaphthalene 10 in 99% yield as an 83 17 mixture of separable diastereomers. Reductive cleavage of 10 by sequential treatment with methyl fluorosulfonate, NaBKi, and aqueous oxalic acid afforded the corresponding enantiopure aldehyde 11 in 88% yield. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

At the beginning of the new millennium, Hashmi et al. presented a broad research study on both intramolecular and intermolecular nucleophilic addition to alkynes and olefins [18]. One of the areas covered by these authors was the isomerization of co-alkynylfuran to phenols [19]. After that, Echavarren and coworkers identified the involvement of gold-carbene species in this type of process, thus opening a new branch in gold chemistry [20]. And subsequently, Yang and He demonstrated the initial activation of aryl —H bonds in the intermolecular reaction of electron-rich arenes with O-nucleophiles [21, 22]. 

The intermediate iis-cyclohexadienyl anionic species from nucleophilic addition to the [(arene)Cr(CO)3] complexes are obviously highly electron rich and should be susceptible to reactions... 

The K-region oxides undergo nucleophilic addition with OH", C032", water, amines, and mercaptides.88,140 The second-order rate constants for the reactions of OH", water, and primary and secondary amines with 1 at 30°C and with ethylene oxide at 25°C141 can be simply related by Eq. (6),2 which shows that the sensitivity of the two oxides to the nature of the nucleophile is similar and that the arene oxide is more reactive. 

Aromatic ketones arylations, 10, 140 asymmetric hydrogenation, 10, 50 G—H bond alkylation, 10, 214 dialkylzinc additions, 9, 114-115 Aromatic ligands mercuration, 2, 430 in mercury 7t-complexes, 2, 449 /13-77-Aromatic nitriles, preparation, 6, 265 Aromatic nucleophilic substitution reactions, arene chromium tricarbonyls, 5, 234... 

Of particular interest is the observation that in certain cases products such as 24 resulting from domino processes are obtained After the formation of the furan, evidently a double Michael-type addition of these intermediates to the remaining starting material 23 can take place at the unsubstituted 5-position. Preliminary experiments to investigate scope and limitations of such addition reactions in the presence of gold salts also confirm the applicability to the functionalization of other electron-rich arenes (Scheme 6) Besides furans, azulene 28 and di- and trialkoxybenzene are suitable as nucleophiles for the reaction with unsaturated carbonyl compounds [14]. For instance, 2-methylfuran (25) reacts at the reactive 5-position with methyl vinyl ketone 26 to give the addition product 27, and with azulene 28 a twofold... 

The second important use of superbases is side-chain alkylation of aromatic compounds [22, 34]. In these reactions a benzyl anion generated by the superbase catalyst subsequently attacks olefins such as ethene or propene as a nucleophile. The result of such a nucleophilic addition of a carbanion is side-chain alkylation of the arene by ethene. The reaction was commercialized by Sumitomo for the side-chain alkylation of cumene (Scheme 5, a) [34]. 

Only one example of an attachment of heteroarenes by addition/elimination strategy has been devised [77, 111]. Although arenes are more or less resistant toward addition, heteroaromatic systems such as isoquinolines 118 are prone to addition of nucleophiles. Subsequent reaction with addition of electrophiles furnishes the so-called Reissert compounds 120. These are stable compounds which can, for example, be alkylated. In solid-phase synthesis the electrophile chosen was a polymer-based acid chloride. Detachment can be achieved by simple addition of hydroxide ions (Scheme 6.1.30). 

Benzene cyclopentadienyl ruthenium(II) complex 125 undergoes nucleophilic addition at the arene ligand via the addition of sodium borohy-dride or phenyllithium. Reaction with phenyllithium gives the exo-phenyl cyclohexadienyl derivative 249 in 89% yield (154) [Eq. (32)]. 

Activation of aromatic compounds by transition-metal complexes was initially studied with Cr(CO)3 complexes. Nucleophilic addition of 2-lithio-l,3-dithianes to arene-chromium(O) complexes 185 followed usually by iodine-promoted decomplexation affords the corresponding 2-arylated 1,3-dithianes 186. The reaction of //-(toluene)- and (anisole)tricarbonylchromium (185) with compound 161 gave mixtures (52 46 and 10 90, respectively) of ortho and meta substituted derivatives (186) (Scheme 54)244. The meta directing effect was also observed (mainly better than 95%) with amino and fluoro substituted complexes245. 

The reaction of FeC or FeCft with AICI3 in an arene solvent, at reflux, results in the formation of the corresponding bis( ( -arene)iron dications (433) (Scheme 109). These dications are susceptible to nucleophilic attack to afford the ( ( -arene)(j( -cyclohexadienyl)iron cations (434). For the bis(mesitylene)iron dication, reaction with two equivalents of a nucleophile sequentially occurs on each of the arene rings to afford bis (j( -cyclohexadienyl)iron complexes (435), in accord with the prediction of the Davies Green Mingos rules (see Davies-Green-Mingos Rules) for nucleophilic addition. More recently, it has been found that reaction of other cations (434) with a variety of nucleophiles, in THF... 

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