Nucleophilic reactions arenes

The photochemical nucleophile-olefin combination aromatic substitution (photo-NOCAS) reaction received considerable attention from many groups not only because of its synthetic value because the yields of nucleophile-olefm-arene (1 1 1) adducts can be high but also because of interesting mechanistic details (Scheme 48). 

Detailed studies by Bruice, Jerina, and co-workers, referred to earlier, showed that three factors determine whether nucleophilic reaction of tissue materials with arene oxides occur directly. They are (a) the structure of the... 

Miyata et al.202 found that the order of mutagenicity of K-region arene oxides tested in Salmonella typhimurium strain TA 98 is 28 > 4 > 354, 254 > 29 > 1, 253, 355. Oxide 28 is most reactive, whereas 4 is also fairly active. In the nucleophilic reactions, 28 is more reactive in general. This fact might be linked to the strong mutagenicity of 28. However, 29, which is... 

Two important reactions of arene oxides in animal tissue are (1) detoxification and (2) formation of conjugates of arene oxides with purine pyrimidine bases of DNA. For both of these reactions to take place, the arene oxide should have a certain intrinsic stability to survive an aromatization reaction. Reaction with the thiolate bond of glutathione is responsible for detoxification, whereas the extent of involvement of arene oxides in the nucleophilic reactions with nonpolarized nitrogen bases of DNA is directly related to their carcinogenic activity. 

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... 

The yellow CpFe1 (//6-arene) salts (most commonly BF4 or PF6 ) are usually stable up to at least 200 °C, are stable in concentrated sulfuric acid, and are very resistant towards oxidation (until recently, it was believed that they could not be oxidized [23] vide infra). They are not easy to reduce either [23] (vide infra). The chloride salts [CpFe+( f -arene) Cl- are water-soluble they are formed upon hydrolysis following ligand-exchange reactions between ferrocene and the arene in the presence of aluminum chloride [21]. Such aqueous solutions may sometimes be directly used for nucleophilic reactions [22] (vide infra). The BF4- salts are also sometimes quite soluble in water, but the PF6- salts are much less so. Electrophilic reactions that are readily undergone by the free arenes, such as Friedel-Crafts reactions, are no longer possible on the CpFe+( /6-arene) complexes [19, 23]. On the other hand, a range of nucleophilic reactions that are impossible or very difficult to carry out with free arenes become possible under ambient or mild conditions with the CpFe+()/6-arene) complexes (Scheme 2) [16-20]. 

Here, either X = (I T2C(0)-R j and ox = Jones reagent or X — CN and ox = CeIv. It has been emphasized that the addition of nucleophiles to (arene)Mn(CO)3+ complexes does not occur through an initial ET from the nucleophile to the metal center [2]. This represents an additional advantage since such redox reactions frequently lead to the decomposition of the metal complex, a typical example being the reductive deligation of bis(arene)Fe2+ complexes [48]. On the other hand, intramolecular charge transfer from the arene to the metal not only induces an electron deficiency in the arene ring (which is critical for effective attack of the nucleophile), but it also results in an attenuation of the electrophilicity of the metal center so as to avoid undesired ET reactions of the metal with the nucleophile. 

Scheme 39 Pathways for reaction of carbon nucleophiles with arene ligands...

The reactions of strong carbon nucleophiles with arene oxides 1 and 11 leads to rapid adduct formation.Methyl lithium and dimethyl magnesium react with arene oxide 1 by 1,6-addition to give ds-adducts. Trans-adducts were also obtained from reaction of dimethyl magnesium and methyl lithium with arene oxides 1 and 11, respectively, by the more usual 1,2-trans addition mechanism. ... 

The SNAr reactions of heteroarenes can be realized in a similar manner, as in the series of arenes [71, 82]. These nucleophilic reactions are analogous to electrochemical Sn transformations of arenes [22, 24, 25]. Terrier and co-workers considered an opportunity for electrochemical methoxylation of 4,6-dinitrobenzofuroxan by action of the methoxide ion via the SnAt mechanism [21]. The intermediate o -complex formed was oxidized successfully into the corresponding substitution product. Analogously, the formation of heteroaromatic amines has been suggested to occur via intermediacy of the corresponding amino adducts, as exemplified by the oxidation of the o -complex derived fi om the reaction of pyrimidine with NH2 (Scheme 26) [3, 102-104]. 

Cr(CO)3 unit in (r -arene)Cr(CO)3 complexes withdraws electrons from the arene ligand making it less susceptible to electrophilic attack than the free arene, but more susceptible to attack by nucleophiles (reaction 24.125). 

Concerning the reaction mechanism, the factors having the profound influence on the reactions are the nucleophilicity of arene and electrophilicity of aryllead(IV) reagent. Electron-donating groups increase an electron-density of the arene, and thus enhance its reactivity. 

The factors that control the site of attack of nucleophiles on arene complexes are complex, and the position of attack is controlled by the electronic properties of the substituents. These properties dictate whether attack will occur meta or para to the substituent. Steric effects discourage attack ortho to the substituent. In many cases, the attack of nucleophiles on coordinated arenes is reversible. Thus, the final productive reaction may result from addition at a site of the arene that is not the kinetic site for attack. For example, nucleophilic attack onto the ortho, meta, or para positions of the phenyl chloride coordinated to Cr(CO)j in Equation 11.53 is reversible, and it is only attack at the ipso position that leads to productive substitution chemistry. - ... 

Thus, SjjAr reaction in halonitrohenzenes can proceed when initially formed a"-adducts are not converted into products of S jArH hut learomatize via dissociation to starting nucleophiles and arenes. This equihbration followed hy slower hut itreversihle (as a rule) addition at positions occupied by halogens X and subsequent departure of X anions fiom the a -adducts results in S Ar reaction. Since... 

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