Electrophilic Pathways

A variety of halide sources have been shown to be capable of displacing the nitro group of the 1,2,4-triazolo[5,l-c][l, 2,4] triazines (180). Unexpectedly, chlorine and bromine in acetic acid gave the same products, presumably via electrophilic pathways (82CHE992). 

GL 2] [R 5] [P 3] By addition of formic acid, the polarity of the solvent can be enhanced, which is known to favor the electrophilic pathway. Using formic acid/ acetonitrile mixtures, conversions of44-77% and yields of 60-78% were obtained for different contents of the solvents and different flow rates [16]. The performance in pure acetonitrile was much lower (conversion, 15% yield, 71%) and was accompanied by fouling of the micro device due to insufficient liquid reactant solubility. 

Similar intramolecular hydroarylations of alkynes and alkenes, which obviate the need for a halide or triflate group on the aryl ring, are now well established. Sames group screened over 60 potential catalysts and over 200 reaction conditions, and found that Ru(m) complexes and a silver salt were optimal. This process appears to tolerate steric hindrance and halogen substrates on the arene (Equations (175)—(177)). The reaction is thought to involve alkene-Ru coordination and an electrophilic pathway rather than a formal C-H activation of the arene followed by alkene hydrometallation, and advocates the necessary cautious approach to labeling this reaction as a C-H functionalization... 

What purpose does the alkane binding to the Pt(II) center serve For the electrophilic pathway (Scheme 5, b), this is immediately apparent, a-Alkane complexes should be considerably more acidic than free alkanes, such that deprotonation may become a viable C-H activation pathway. While the acidic character of alkane complexes has not been directly observed, it can be inferred from the measured acidity of analogous agos-tic complexes (36) and from the acidity of the a-complexes of dihydrogen (37), both of which can be regarded models for alkane complexes (see Section III.E). 

Fig. 4. Relevant structures for the discussion of methane activation by (bipyrimi-dine)PtCl2 Methane complex of Pt(II) (A) methyl(hydrido)platinum(IV) complex, the product of the oxidative addition (B) transition state for intramolecular deprotonation of the methane complex ( cr-bond metathesis , sometimes also called electrophilic , C) intermolecular deprotonation of the methane complex ( electrophilic pathway , D).

Phosphine complexes are generally regarded more electron-rich than the corresponding ammine complexes, and which pathway is preferred under these electronic conditions has also been investigated. For trans-PtCl2(PH3)2, oxidative addition has been calculated to be much more favorable than the electrophilic pathway for the activation of methane... 

Radical hydroxylation of hydrocarbons by autooxidation yields alcohols (major products), ketones, and acids (minor products). Cyclohexanol, for example, is formed in 90% yield from cyclohexane and peroxyacetic acid (275). The high -ol/-one ratio at low conversions can sometimes be used as a partial diagnostic tool to distinguish between the radical and electrophilic pathways. The predominant reaction of electrophilic radicals, such as HO, ROO, and CH 3 is H-atom abstraction from reactants (S-H) or peracids, as exemplified by the following ... 

The addition of thiols to C—C multiple bonds may proceed via an electrophilic pathway involving ionic processes or a free radical chain pathway. The main emphasis in the literature has been on the free radical pathway, and little work exists on electrophilic processes.534-537 The normal mode of addition of the relatively weakly acidic thiols is by the electrophilic pathway in accordance with Markovnikov s rule (equation 299). However, it is established that even the smallest traces of peroxide impurities, oxygen or the presence of light will initiate the free radical mode of addition leading to anti-Markovnikov products. Fortunately, the electrophilic addition of thiols is catalyzed by protic acids, such as sulfuric acid538 and p-toluenesulfonic acid,539 and Lewis acids, such as aluminum chloride,540 boron trifluoride,536 titanium tetrachloride,540 tin(IV) chloride,536 540 zinc chloride536 and sulfur dioxide.541... 

The efficiency of /-elements in catalysis originates from unconventional electrophilic pathways. In contrast to rf-elements oxidative addition/reductive elimination sequences are not accessible. Instead, substrate adduct formation, ligand exchange and insertion reactions rule the mechanistic scenarios. Therefore, the main emphasis is put on the fine-tuning of the spectator ligand of the precatalyst. 

Another instructive scenario may be found when considering the metalation of arenes. There are two distinct mechanisms for the metalation of aromatic C-H bonds - electrophilic substitution and concerted oxidative addition (Box2). The classical arene mercuration, known for more than a century, serves to illustrate the electrophilic pathway whereas the metal hydride-catalyzed deuterium labeling of arenes document the concerted oxidative addition mechanism [8, 17]. These two processes differ both in kinetic behavior and regioselectivity and thus we may appreciate the need to differentiate these two types of process. However, the choice of C-H bond activation to designate only one, the oxidative addition pathway, creates a similar linguistic paradox. Indeed, it is hard to argue that the C-H bond in the cationic cr-complex is not activated. 

Electron Tran r versus Electrophilic Pathways for Aromatic Substitution... 

The activation of C-H bonds by an electrophilic pathway is shown schematically in eq. (12) and has been observed with a number of late transition metal ions [9], A driving force for the reaction shown in eq. (12) is the stabilization of the leaving group, H", by solvation in polar solvents. The related four-center electrophilic activation by transition, lanthanide, and actinide metal centers has also been reported, (eqs. (13a) and (13b)) [9b,c,g, 27]. In these instances, a ligand on the metal assists the reaction by acting as the base. 

In aromatic chemistry, there is one electrophilic pathway that predominates. This is called the arenium ion mechanism. It occurs in three steps. The first is the formation of the attacking electrophile the second is the attack by this electrophile on the aromatic ring and the third is the departure of an electrofuge, which is usually a proton, with the assistance of a base. Write down the general equations for this sequence of reactions. 

Scheme 2.97 The mechanism of the perfluoroalkylation of oxidizable nucleophiles (e.g. Nu = [Me2CNO2] ) by perfluoroalkyl halides mimics an electrophilic pathway, i.e. nucleophilic substitution (Spi) of the halide [7].

The data in Table I show that the coupling pathway to nitration gives a different ratio of nitro isomers than given by the other, electrophilic pathways. Eberson and Radner (19) have pointed out also that the coupling results can be correlated, but only partly with expectations based on the distribu-... 

Remarkable similarity in rate constants for methane and methanol under the action of the platinum(II) ion has been observed the ratio of rate constants for methane versus methanol oxidations is 0.17. The methyl group of ethanol is oxidized to produce 1,2-ethanediol as the predominant product. The electrophilic pathway of the activation of C-H compounds is presented in Scheme VIII. 8 [45a]. 

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