Base-assisted deprotonation mechanism

The order of reactivity for the reaction sites of azole compounds in electrophilic reactions is known to be 5 >4> 2 [18]. Thus arylation at the relatively electron-rich 5-position may be regarded as similar to that of pyrroles, furans, and thiophenes (Scheme 1). In contrast, the reaction at the 2-position may be regarded as proceeding differently [3], Although the precise mechanism is still unclear, it may involve base-assisted deprotonative palladation with the ArPd(II) species (path d in Scheme 2). Insertion of the C=N double bond into the Ar-Pd bond is also a possi-... 

Recently, the crystal structure of one such SMOMT from alfalfa, isoflavone OMT (IOMT), was solved.37 The likely reaction mechanism of this OMT, deduced from the crystal structure, involves the base-assisted deprotonation of the acceptor s hydroxyl group, followed by a nucleophilic attack by the subsequent phenolate anion on the reactive methyl group of SAM. Modeling of related SMOMTs using the crystal structure of IOMT has also proven useful in understanding the evolution of... 

As an alternative to the classical reaction mechanism, they investigated the possibility of a direct deprotonation of the y5-agostic insertion product by the amine base, which is usually required for successful Heck coupling reactions. The new proposal actually replaces the last two steps of the classical catalytic cycle, P-Vi elimination and base-assisted reductive elimination of HX (Scheme 2). 

The structural and kinetic data suggest a mechanism in which the first phosphoryl transfer step occurs by attack of the nitrogen atom of histidine accompanied by general acid assistance by the Asp carboxyl group. A logical assumption is that the carboxylate form of the Asp residue then acts as a general base to deprotonate a nucleophilic water molecule in the second step, which is hydrolysis of the phosphohistidine intermediate (Figure 8). 

The mechanism of direct arylation has been studied experimentally and computationally and possible pathways include electrophilic aromatic substitution, Heck-type coupling and concerted metalation-deprotonation (CMD). The reaction pathway is dependent on the substrate and the catalytic system employed,however, most electron-rich (hetero)arenes seem to follow a base-assisted CMD pathway. Two catalytic cycles for the coupling of bromo-benzene and thiophene are shown in Schemes 19.5 and 19.6. Scheme 19.5 depicts a carboxylate-mediated process where C-H activation occurs... 

Most of the mechanisms for heteroaromatic C—H bond activation by a transition-metal catalyst fall into one of these four categories (i) electrophilic aromatic metala-tion, (ii) carboxylate-ligand-promoted concerted metalation-deprotonation (CMD), (iii) base-assisted metalation and (iv) oxidative addition of C—H to the metal center. The type of mechanism operating in the cleavage of the C—bond depends on the electronics of the heterocycle (and therefore its substituents) and the reaction conditions being employed. 

In some of the mechanisms shown in the answers, a series of protonations and deprotonations occur. These steps convert the initial tetrahedral intermediate into an intermediate that more easily loses a leaving group. These deprotonations may be brought about by the solvent, by the conjugate base of the catalyst, by other molecules of the carbonyl compound or may occur intramolecularly. When a "proton transfer" is shown as part of a mechanism, the base that removes the proton has often not been shown. However, it is implied that the proton transfer is assisted by a base the proton doesn t fly off the intermediate unassisted. 

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