Deprotonation, base-assisted

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... 

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

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). 

As stated above, Knoevenagel condensations can occur on catalysts combining acidic and basic sites. A well-known system is the combination of an amine and its carboxylic acid salt. Such catalysts seem to activate the carbonyl substrates, usually by imine or enamine formation, and the activated substrate is subsequently activated by protonation. The base assists the deprotonation of a methylene-active compound, forming a carbanion, followed by nucleophilic attack on the proto-nated imine (Scheme 3A). 

The possibilities for the formation of carbon—carbon bonds involving aromatic compounds have been enormously enhanced by the use of transition metal catalysts, and this area has been the subject of several reviews. Some of these concentrate on the applications of specific metals, and there have been surveys of the use of compounds of silver, copper and nickel,mthenium, and palladium in catalysis. The metalation of carbon-hydrogen bonds, preceding functionalization, may be aided by carboxylate ions, and this subject has also been reviewed. There is evidence here for concerted base-assisted deprotonation as shown in (10). In the carboxylate-assisted reaction of aryl ketimines with alkyl halides, a ruthenium-bonded intermediate (11) has been proposed, which subsequently adds the alkyl halide. " ... 

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... 

It was considered that the reaction initiated by dehydrogenation of pyridyl methanol through base-assisted deprotonation of the OH group/Ru-catalyzed P-hydride elimination led to the corresponding aldehyde. Aldol condensation of the... 

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. 

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

Addition of such a-lithiosulfinyl carbanions to aldehydes could proceed with asymmetric induction at the newly formed carbinol functionality. One study of this process, including variation of solvent, reaction temperature, base used for deprotonation, structure of aldehyde, and various metal salts additives (e.g., MgBrj, AlMej, ZnClj, Cul), has shown only about 20-25% asymmetric induction (equation 22) . Another study, however, has been much more successful Solladie and Moine obtain the highly diastereocontrolled aldol-type condensation as shown in equation 23, in which dias-tereomer 24 is the only observed product, isolated in 75% yield This intermediate is then transformed stereospecifically via a sulfoxide-assisted intramolecular 8, 2 process into formylchromene 25, which is a valuable chiron precursor to enantiomerically pure a-Tocopherol (Vitamin E, 26). 

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