Reactions metallation/ electrophilic substitution

No complete study on the mechanism of halogenation of metal acetyl-acetonates has been carried out. Although the halogenating agents used in these reactions can form the 3-halo compounds via a radical or ionic mechanism, it seems reasonable to assume that these reactions are electrophilic substitution reactions. The probable mechanism is as follows (49, 112) the chelate ring undergoes Sn2 attack by the electrophile ... 

Reactions involving electrophilic substitution of hydrogen in arenes are known for both nontransition [Hg(II), Tl(III), Pb(IV)] and transition metals [Au(III), Pd(II), Pt(IV)] [49]. Pd(II)-catalyzed acetoxylation involves arene activation via formation of an organometallic aryl-Pd c-complex followed by oxidative addition of oxidant and reductive elimination to restore Pd(II) and release the product [11, 50]. Without oxidant, coupling reactions predominate, suggesting arylpalladium(IV) and arylpalladium(II) intermediates in the routes leading to aryl acetates and biaryls, respectively (Scheme 14.10). 

Generally, one may state that the PES of the reaction of electrophilic substitution in the region of a transition state is much simplified as compared with the nucleophilic substitution. Therefore, the effects of solvation and small amounts of catalysts, particularly those coordinating the metal centers in XXIV, may considerably exceed the magnitude of the above-examined structural effects. One may appropriately point to the calculations on the hydrated methonium ion performed by the CNDO/2 method with a special parametrization in super-molecular approximation, and with the surrounding of 5 and 10 water molecules taken into account. They led to the conclusion that the pyramidal C4V structure, rather than the structures or Dj, is in solution energetically the most favored [83]. The structure of the first hydrated shell is shown by the formula XXVI ... 

Polysubstituted benzenes are widely used both in industry and in research laboratories. Regioselective construction of polysubstituted benzenes is usually achieved through the gradual introduction of substituents in the aromatic ring by Friedel-Crafts reaction or similar reactions of electrophilic substitution or through organometallic synthesis. In 1948, Reppe reported the [2+2+2] trimerization of substituted acetylenes in the presence of transition metals to form polysubstituted benzenes (Scheme 1.1) [1]. 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

The most notable chemistry of the biscylopen-tadienyls results from the aromaticity of the cyclopentadienyl rings. This is now far too extensively documented to be described in full but an outline of some of its manifestations is in Fig. 25.14. Ferrocene resists catalytic hydrogenation and does not undergo the typical reactions of conjugated dienes, such as the Diels-Alder reaction. Nor are direct nitration and halogenation possible because of oxidation to the ferricinium ion. However, Friedel-Crafts acylation as well as alkylation and metallation reactions, are readily effected. Indeed, electrophilic substitution of ferrocene occurs with such facility compared to, say, benzene (3 x 10 faster) that some explanation is called for. It has been suggested that. 

Furthermore, the strongly metallic character of selenium weakens the C-Se bond and thus favors reactions involving opening of the ring. The basicity of the three heterocycles is approximately in the same order, the nitrogen atom of selenazole and thiazole possessing much the same properties as the heteroatom of pyridine. Of the two carbon atoms ortho to nitrogen, that is, the 2-carbon and the 4-carbon, only the one in the 2-position is fairly active as a result of its interaction with selenium or sulfur. The 4- and 5-positions of thiazole and selenazole are more susceptible to electrophilic substitution than the 3- and 5-positions of pyridine. This is particularly true of the 5-position of selenazole. Thus it can be said that the 2- and 5-positions of the selenazoles and thiazoles... 

The reactions in this chapter are arranged in order of leaving group hydrogen, metals, halogen, and carbon. Electrophilic substitutions at a nitrogen atom are treated last. 

Rosenblum M, Abbate FW (1966) The problem of metal atom participation in electrophilic substitution reactions of the iron group metallocenes. J Am Chem Soc 88 4178 184... 

Its aromaticity cannot, of course, be tested by attempted electrophilic substitution, for attack by X would merely lead to direct combination with the anion. True aromatic character (e.g. a Friedel-Crafts reaction) is, however, demonstrable in the remarkable series of extremely stable, neutral compounds obtainable from (15), and called metallocenes, e.g. ferrocene (16), in which the metal is held by n bonds in a kind of molecular sandwich between the two cyclopentadienyl structures ... 

New electrophilic substitution reaction methods for the preparation of dipyrromethanes have been reported. The condensation of IV-methylpyrrole with benzaldehyde leading to the corresponding dipyrromethane was promoted by the addition of the organic catalyst, pyrrolidinium tetrafluoroborate <06T12375>. The reaction between pyrrole and N-tosyl imines promoted by metal triflates gave dipyrromethanes whereas tripyrromethane byproducts were not observed <06T10130>. 

The chemistry of diazines remains an area of intense interest, both academic and industrial, with applications in many areas, from biomedical to materials science and electronics. They are versatile, having very varied reactivity, giving many opportunities for manipulation of substituents. Nucleophilic substitutions, electrophilic substitution in oxy and amino derivatives, organometallic and transition metal-catalysed coupling reactions are all subjects of substantial research effort. There are obvious similarities in reactivity of the three diazine systems but also many interesting and practically important, often subtle, differences. 

Metallation reactions at C4 of sydnones and sydnonimines are used as a means of achieving electrophilic substitution. Examples that have appeared since the last review of the subject <1996CHEC-II(4)165> are given in Section 5.03.7.1.1. 

Thus, metalation of cyclic nitrones, followed by successive reactions with electrophilic reagents serves as a synthetic method toward a-heteroatom substituted nitrones, which are inaccessible by other methods. It is noteworthy that these reactions can take place only with cyclic nitrones with E -configuration of the aldonitrone group. 

Chiral Hydrazone Systems. In 1976, Corey and Enders34 demonstrated the great synthetic potential of metalated dimethylhydrazones as highly reactive intermediates in regio- and diastereoselective C C bond formation reactions. The procedure for carrying out the electrophilic substitution reaction... 

To summarize, electrophilic substitutions and metalations of thiophenes take place preferably at the a-positions due to the electronegativity of the sulfur atom. This is the consequence of the more effective incorporation of lone pair electrons on the sulfur into the aromatic system. Although regioselective reactions are routinely performed for oc,p-dihalofurans, regioselectivity is not as easily achieved in Pd-mediated chemistry with oc,p-dihalothiophenes. 

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