Arens substitution mechanism

In equation (256), haloacetylene and nucleophile could be eliminated and these could form the substitution products by addition-elimination steps, the IIT mechanism or the Arens process. By using LiNRJ as a base in equation (255) and looking for two ynamines, or by adding ArSH to reaction (256) and looking for two thioether products, one can seek evidence of the elimination process. Until such tests are performed, the applicability of the Viehe substitution mechanism remains uncertain. 

The catalytic oxidative coupling of two dissimilar arenes is also possible, for example, iV-acetyl indoles, or benzofurans, with benzene and other simple arenes. The mechanism involves sequential metallations in the two rings. The regioselectivity can be controlled by the choice of oxidant, Cu(OAc)2 favouring C-3 and AgOAc, C-2 substitution in 1-acetylindole. ... 

Figure 10.26 A common mechanism by which arenes substituted with nitrogen at various oxidation stales can become mutagens. This scheme is highly simplified—other fates might also await the various arenes shown.

The dissociative loss of a ligand in the first step allows the arene to n complex with the metal. In support of the electrophilic substitution mechanism it has been shown (49) that electron-donating substituents on the ring enhance the rate of ortho substitution. In the above example, this would be consistent with the attack of the electrophile Ru2+ in the n complex to form the a complex which is then stabilized by proton transfer (oxidation) to form the dihydrido species. The essential steps in the reaction sequence are all reasonable and each is more or less documented and hence there is good reason to believe that H—D exchange occurs essentially in the manner shown. 

As before, the exploration of the metal-free oxidative amination was a competitive process. Both Chang" and Antonchick" simultaneously discovered nearly identical I(III)-mediated aminations. They both proposed that the reactions operated by generating an electrophilic nitrogen source in situ. This new species then acted as an R2N equivalent and aminated the arene via an electrophilic aromatic substitution mechanism. This hypothesis seemed appealing, but their data could not be directly compared to ours, as neither Chang nor Antonchick performed reactions on arene substrates that could provide mixtures of regiomers (e.g., toluene). 

The reactions of HTIB with alkenes (Scheme 3.73) can be rationalized by a polar addition-substitution mechanism similar to the one shown in Scheme 3.70. The first step in this mechanism involves electrophilic flnfi-addition of the reagent to the double bond and the second step is nucleophilic substitution of the iodonium fragment by tosylate anion with inversion of configuration. Such a polar mechanism also explains the skeletal rearrangements in the reactions of HTIB with polycyclic alkenes [227], the participation of external nucleophiles [228] and the intramolecular participation of a nucleophilic functional group with the formation of lactones and other cyclic products [229-231]. An analogous reactivity pattern is also typical of [hydroxy(methanesulfonyloxy)iodo]benzene [232] and other [hydroxy(organosulfonyloxy)iodo]arenes. 

In contrast to the oxidative addition mechanism proposed by Chatt several researchers, based on their observations for C H bond activation of unactivated alkanes and (hetero)arenes, proposed an electrophilic substitution mechanism to be operating in such systems. Besides the two types of mechanisms mentioned above, few others have also been suggested and will be discussed in details in the subsequent sections. 

The 19-electron complex [Fe Cp(ri -toluene)] undergoes uncatalyzed arene substitution by P(Me)3 ligands. What is the final reaction product The kinetic studies of these reactions show that they proceed according to the associative mechanism. Why does the mechanism imply a pre-dissociation to the 17-electron species [Fe Cp(T] -arene)] (J. Ruiz et al., J. Am. Chem. Soc.. 1990, 772,5471). 

Photonucleophilic aromatic substitution reactions of phenyl selenide and telluride with haloarenes have also been proven to involve the S jlAr mechanism, with the formation of anion radical intermediates. Another photonucleophihc substitution, cyanomethylation, proves the presence of radical cations in the reaction mechanism. Liu and Weiss have reported that hydroxy and cyano substitution competes with photo substitution of fluorinated anisoles in aqueous solutions, where cation and anion radical intermediates have been shown to be the key factors for the nucleophilic substitution type. Rossi et al. have proposed the S j lAr mechanism for photonucleophihc substitution of carbanions and naphthox-ides to halo anisoles and l-iodonaphthalene. > An anion radical intermediate photonucleophilic substitution mechanism has been shown for the reactions of triphenyl(methyl)stannyl anion with halo arenes in liquid ammonia. Trimethylstannyl anion has been found to be more reactive than triphenylstannyl anion in the photostimulated electron- transfer initiation step. 

Arene oxides can be intermediates in the bacterial transformation of aromatic compounds and initiate rearrangements (NIH shifts) (Dalton et al. 1981 Cerniglia et al. 1984 Adriaens 1994). The formation of arene oxides may plausibly provide one mechanism for the formation of nitro-substituted products during degradation of aromatic compounds when nitrate is present in the medium. This is discussed in Chapter 2. 

It seems that no general mechanistic description fits all these experiments. Some of the reactions proceed via an addition-elimination mechanism, while in others the primary step is electron transfer from the arene with formation of a radical cation. This second mechanism is then very similar to the electrochemical anodic substitution/addition sequence. 

Haloarenes have been found to undergo nucleopilic substitution when irradiated with the triphenyl stannyl anion46, reacting via a radical S l mechanism. In many cases the reaction will only occur under photochemical conditions. The reaction is found to proceed with chloro- and bromo-substituted arenes, but not iodo-compounds. The anion is produced either by treatment of triphenyltin chloride or hexaphenylditin with sodium metal in liquid ammonia, and will react with a wide variety of arenes (reaction 30). 

Gold catalysts are employed in the arylation of aryl-substituted terminal alkynes (Scheme 18).73 Two different mechanisms are postulated. The first step can be the auration of the arene by gold(m) chloride, generating an arylgold... 

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