Carbon-hydrogen bonds electrophilic reactions

A review has been published regarding computational studies of arenes, linear polycyclic aromatics, and their reactivities in electrophilic and nucleophilic processes. There have also been reviews of theoretical studies of electron delocalization and its relevance to electrophilic substitution, and of mechanisms of activation of carbon-hydrogen bonds to reactions with electrophiles. ... 

The occurrence of a hydrogen isotope effect in an electrophilic substitution will certainly render nugatory any attempt to relate the reactivity of the electrophile with the effects of substituents. Such a situation occurs in mercuration in which the large isotope effect = 6) has been attributed to the weakness of the carbon-mercury bond relative to the carbon-hydrogen bond. The following scheme has been formulated for the reaction, and the occurrence of the isotope effect indicates that the magnitudes of A j and are comparable ... 

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

A second process that has a central position in the analysis of the chemical properties of carbenes is their reaction with hydrocarbons. As is the case for alcohols, singlet and triplet carbenes react with hydrocarbons in distinctive ways. It has long been held that very electrophilic singlet carbenes can insert directly into carbon-hydrogen bonds (11) (Kirmse, 1971). On the other hand, triplet carbenes are believed to abstract hydrogen atoms to generate radicals that go on to combine and disproportionate in subsequent steps (12)... 

Indeed, it has recently been shown by Rozen [13] that tertiary carbon-hydrogen bonds can be selectively replaced by carbon-fluorine bonds when the reaction is carried out in a polar solvent at low temperature,but it was suggested that an electrophilic process involving a carbocationic transition state is occuring in these instances (see 3.1.1.1). 

Apparently, the discrepancies detected for the substitution data are largely the consequence of a multiplicity of minor influences operative in the transition state. The deviations are sufficiently diverse in character to require the significance of additional influences on the stability of the transition state. Four other important factors are complexing of the substituent with the electrophilic reagent or catalyst, the involvement of 7r-complex character in the transition state for the reaction, rate effects originating in the rupture of carbon-hydrogen bonds, and differential solvation of the electron-deficient transition states. 

Redistribution of electron density in CT complexes results in a modification of the chemical properties of coordinated arenes, and this effect is widely used in organometallic catalysis [2]. To demonstrate the relationship between charge transfer in arene complexes and their reactivity, we focus our attention on carbon-hydrogen bond activation, nucleophilic/ electrophilic umpolung, and the donor/acceptor properties of arenes in a wide variety of organometallic reactions. 

Since the observation that Rh(II) carboxylates are superior catalysts for the generation of transient electrophilic metal carbenoids from a-diazocar-bonyls compounds, intramolecular carbenoid insertion reactions have assumed strategic importance for C-C bond construction in organic synthesis [1]. Rhodium(ll) compounds catalyze the remote functionalization of carbon-hydrogen bonds to form carbon-carbon bonds with good yield and selectivity. These reactions have been particularly useful in the intramolecular sense to produce preferentially five-membered rings. 

Mercury salts can react directly with hydrocarbons exchanging hydrogen for mercury. This reaction is an electrophilic substitution (equation 5) and hence can take place with arenes, cyclopentadienyls, terminal aUcynes, and also with aliphatic hydrocarbons that contain activated carbon-hydrogen bonds (e.g. carbonyl or nitrile compoimds). When the hydrocarbon contains several equivalent hydrogen atoms, polymercuration is often observed. 

This interpretation is consistent with our mechanism. The rate of the overall substitution is determined by the slow attachment of the electrophilic reagent to the aromatic ring to form the carbonium ion. Once formed, the carbonium ion rapidly loses hydrogen ion to form the products. Step (1) is thus the rate-determining step. Since it docs not involve the breaking of a carbon- hydrogen bond, its rate- and hence the rate of the overall reaction- is independent of the particular hydrogen isotope that is present. 

Treatment of an alkene with mercuric acetate in aqueous THF results in the electrophilic addition of mercuric ion to the double bond to form an intermediate mercuri-um ion. Nucleophilic attack by H2O at the more substituted carbon yields a stable organomercury compound, which upon addition of NaBH4 undergoes reduction. Replacement of the caiton-mercury bond by a carbon-hydrogen bond during the reduction step proceeds via a radical process. The overall reaction represents Markovnikov hydration of a double bond, which contrasts with the hydroboration-oxidation process. 

The electron-deficient sulfonyl nitrene (88) can insert into electron-rich carbon-hydrogen bonds, abstract hydrogen atoms, and add to double bonds and aromatic rings. These reactions may be initiated by acids, heat, light and transition metals. The reactions are illustrated by heating methanesulfonyl azide (89) with bezene (23) (Scheme 59). Here, the electrophilic sulfonyl nitrene (90) adds to the electron-rich aromatic double bond, but the kinetically favoured azepine(91) rearranges to give the thermodynamically favoured N-phenyl sulfonamide (92) (Scheme 59). 

The positively charged carbon atom in a carbocation is an extremely electron-dehcieni (electrophilic) carbon. As such, its behavior is dominated by a need to obtain an electron pair from any available source. The Sn I reaction illustrates the most obvir>"s fate of a < nr .- -t on c a.bination with an external Lewis base, forming a new bond to carbon. However, the electron deficiency of cationic carbon is so great that even under typical SnI solvolysis conditions, surrounded by nucleophilic solvent molecules, some of the cations won t wait to combine with external electron-pair sources. Instead, they will seek available electron pairs within their own molecular structures. The most available of the.se are electrons in carbon-hydrogen bonds one carbon removed from the cationic center (at llic so-called carbon) ... 

The electrophilic substitution reactions involving imidoyl halides are centered around the displacement on carbon-hydrogen bonds. For example,... 

This chapter presents developments in the activation and functionalization of carbon-hydrogen bonds that have been discovered since 1993. Major breakthroughs in hydrocarbon activation appeared in the early 1980s, and in the following decade, an explosion of discoveries was seen in new examples of metal complexes that could activate C-H bonds. Mechanisms for cleavage included oxidative addition, electrophilic cleavage, radical H-abstraction, and metal atom reactions, and several texts are available that summarize the first decade of this work. " ... 

C.i.a. Sequential Hydroarylation (Hydroalkenylation)/Cyclization. Since the cis stereochemistry of addition pushes the substituents of the acetylenic moiety to the same side of the olefinic double bond, a cyclization reaction can follow the addition step when these substituents bear suitable nucleophilic and electrophilic centers, and the whole process resembles a valuable straightforward methodology for the preparation of cyclic compounds (Scheme 20). Cyclization can occur under hydroarylation(hydroalkenylation) conditions—either before or after the substitution of the carbon-hydrogen bond for the carbon-palladium bond—or by subjecting the isolated hydroarylation(hydroalkenylation) product to suitable reaction conditions. This strategy has been employed successfully to develop new routes to various heterocycles. 

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