Lewis acids cationic intermediates

Most solid-phase syntheses of pyrazoles are based on the cyclocondensation of hydrazines with suitable 1,3-dielectrophiles. The reported examples include the reaction of hydrazines with support-bound a,(3-unsaturated ketones, 1,3-diketones, 3-keto esters, a-(cyano)carbonyl compounds, and a, 3-unsaturated nitriles (Table 15.19). Pyrazoles have also been prepared from polystyrene-bound 3-(hydrazino)esters, which are generated by the addition of ester enolates to hydrazones (Entry 7, Table 15.19 see also Section 10.3). Benzopyrazoles can be prepared from support-bound hydra-zones using the reaction sequence outlined in Figure 15.11. Oxidation of a polystyrene-bound benzophenone hydrazone yields an a-(acyloxy)azo compound. Upon treatment with a Lewis acid, this intermediate is converted into a 1,2-diazaallyl cation,... 

In Summary The problems of Friedel-Crafts alkylation (multiple substitution and carboca-tion rearrangements) are avoided in Friedel-Crafts acylations, in which an acyl halide or carboxylic acid anhydride is the reaction partner, in the presence of a Lewis acid. The intermediate acylium cations undergo electrophilic aromatic substitution to yield the corresponding aromatic ketones. 

Friedel-Crafts (Lewis) acids have been shown to be much more effective in the initiation of cationic polymerization when in the presence of a cocatalyst such as water, alkyl haUdes, and protic acids. Virtually all feedstocks used in the synthesis of hydrocarbon resins contain at least traces of water, which serves as a cocatalyst. The accepted mechanism for the activation of boron trifluoride in the presence of water is shown in equation 1 (10). Other Lewis acids are activated by similar mechanisms. In a more general sense, water may be replaced by any appropriate electron-donating species (eg, ether, alcohol, alkyl haUde) to generate a cationic intermediate and a Lewis acid complex counterion. 

The mechanism of the cycloaddition reaction of benzaldehyde 2a with Danishefsky s diene 3a catalyzed by aluminum complexes has been investigated theoretically using semi-empirical calculations [14]. It was found that the reaction proceeds as a step-wise cycloaddition reaction with the first step being a nucleophilic-like attack of Danishefsky s diene 2a on the coordinated carbonyl compound leading to an aldol-like intermediate which is stabilized by interaction of the cation with the oxygen atom of the Lewis acid. The next step is the ring-closure step, giving the cycloaddition product. 

Honk et al. concluded that this FMO model imply increased asynchronicity in the bond-making processes, and if first-order effects (electrostatic interactions) were also considered, a two-step mechanisms, with cationic intermediates become possible in some cases. It was stated that the model proposed here shows that the phenomena generally observed on catalysis can be explained by the concerted mechanism, and allows predictions of the effect of Lewis acid on the rates, regioselectivity, and stereoselectivity of all concerted cycloadditions, including those of ketenes, 1,3-dipoles, and Diels-Alder reactions with inverse electron-demand [2],... 

Depending on the specific reaction conditions, complex 4 as well as acylium ion 5 have been identified as intermediates with a sterically demanding substituent R, and in polar solvents the acylium ion species 5 is formed preferentially. The electrophilic agent 5 reacts with the aromatic substrate, e.g. benzene 1, to give an intermediate cr-complex—the cyclohexadienyl cation 6. By loss of a proton from intermediate 6 the aromatic system is restored, and an arylketone is formed that is coordinated with the carbonyl oxygen to the Lewis acid. Since a Lewis-acid molecule that is coordinated to a product molecule is no longer available to catalyze the acylation reaction, the catalyst has to be employed in equimolar quantity. The product-Lewis acid complex 7 has to be cleaved by a hydrolytic workup in order to isolate the pure aryl ketone 3. 

The electrophile 4 adds to the aromatic ring to give a cationic intermediate 5. Loss of a proton from 5 and concomitant rearomatization completes the substitution step. Subsequent hydrolysis of the iminium species 2 yields the formylated aromatic product 3. Instead of the highly toxic hydrogen cyanide, zinc cyanide can be used. The hydrogen cyanide is then generated in situ upon reaction with the hydrogen chloride. The zinc chloride, which is thereby formed, then acts as Lewis acid catalyst. 

The sulfonylation mechanism involves a two-stage reaction, as shown in Scheme 6.4. The sulfonylium cation ArS02+ attacks the carbon on the aromatic nucleus to generate an intermediate complex, which subsequently decomposes to afford the final product by eliminating a proton. It is postulated that the effective sulfonylating agent is the sulfonylium salt generated by action of the Lewis-acid catalyst on the sulfonyl halide.18... 

In contrast, the reaction of 147 with 1, in the absence of catalyst, affords traces of adduct after 3 days. The activation by I2 is due to the formation of cationic iodolactonization intermediate 148 (Scheme 4.28) which reacts easily with the diene, affording the dihydrooxazole 149 which is then treated with Bu N to give the final adduct. With some substrates, this method of activation was proved to be more effective than the use of Lewis acids. 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Metal cations can lend electrophilic assistance to weaken the Pd—X bonds in the intermediate R-Pd —X. Either full fission of this bond, leading to the realization of a polar mechanism, or partial polarization, might take place. Soft Lewis acids (the cations of Cu, Ag, Tl) are used most often (see Chapter 9.8 for a discussion of how metal ions act as Lewis-acid catalysts). 

Early attempts to fathom organic reactions were based on their classification into ionic (heterolytic) or free-radical (homolytic) types.1 These were later subclassified in terms of either electrophilic or nucleophilic reactivity of both ionic and paramagnetic intermediates - but none of these classifications carries with it any quantitative mechanistic information. Alternatively, organic reactions have been described in terms of acids and bases in the restricted Bronsted sense, or more generally in terms of Lewis acids and bases to generate cations and anions. However, organic cations are subject to one-electron reduction (and anions to oxidation) to produce radicals, i.e.,... 

It is very likely, that this reaction occurs due to the equilibrium between trimethylsilyl halide and a nitrogen-containing nucleophile, which increases the electrophilicity of silyl Lewis acids. It should be noted that the configuration of stereocenters at the carbon atoms of the oxazine ring is partially distorted. Hence, it is assumed that the reaction proceeds through the intermediate cation B, which is partially isomerized into the stereoisomeric cation B through the open chain cation B". 

The probable pathway resulting in the stereoselective formation of silylated ene nitrile (586) from enoxime (584) is presented on the right of Scheme 3.282. At higher temperature, the latter eliminates trimethylsilanol to give ene-nitrile (586) under the action of silyl Lewis acid (TfOSiMe3). Evidently, the reaction of compound (585) with TfOSiMe3 at room temperature involves initial silylation of the nitrogen atom to form the cationic intermediate B, which is deprotonated with triethylamine, followed by the thermodynamically favorable l,3-N,C-shift... 

Suitably protected glycosyl halides or acetates, upon Lewis-acid promoted SN1 heterolysis, generate glycosyl cation intermediates that can react with electron-rich arenes, heteroarenes, Me3SiCN, enoxysilanes, enamines, allyl silanes and stannanes, acetylenyl silanes and stannanes affording C-glycosyl compounds. 

The product ratio of 8K/9K is similar to that of the Lewis acid-mediated reaction of 4a-c. These products of the C2-C3 bond cleavage (8K and 9K) may be formed via alkylideneallyl cation intermediate, which is formed by the oxygen protonation of 4. Thus, the product ratio of 10/(8K + 9K) is controlled by the protonations at the olefinic carbon and at the acetal oxygen of 4. 

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