Lewis acids reaction mechanisms

Allyltrialkylsilanes add to aldehydes in the presence of a Lewis acid." The mechanism of this reaction has been examined." " When chiral titanium complexes are used in the reaction, allylic alcohols are produced with good asymmetric... 

The preparation of dioxolanes has been reported by the condensation of oxiranes with a carbonyl compound under neutral conditions and in the presence of Lewis acids the mechanism of the reaction has been studied in detail. Equation 200 depicts the general scheme of the reaction. 

Lectka et al. have reported that Tol-BI NAP-coordinated CUCIO4 catalyzes fhe addition of SEE to a-N-tosylimino esters wifh high enantioselectivity (Scheme 10.81) [227]. The use of a-substituted SEE gives anti adducts wifh high diastereoselectivity. The Tol-BINAP complex is superior to fhe corresponding BINAP complex in diastereo- and enantioselectivity. It has been proposed that this asymmetric Mannich-type reaction proceeds by a Lewis acid-catalyzed mechanism, not a transmetalation mechanism as reported by Sodeoka et al. 

Halogenation (Section 22.1 A) The electrophile is a halonium ion formed as an ion pair by interaction of chlorine or bromine with a Lewis acid. The mechanism involves an initial reaction between Clj and FeClj to generate a molecular complex that can rearrange to give a C1+, FeCl " ion pair. The C1+ reacts as a very strong electrophile with the weakly nucleophilic aromatic 77 cloud to form a resonance-stabilized cation intermediate that loses a proton to give the aryl chloride product. 

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

The mechanism by which Lewis-acids can be expected to affect the rate of the Diels-Alder reaction in water is depicted in Scheme 2.6. The first step in the cycle comprises rapid and reversible coordination of the Lewis-acid to the dienophile, leading to a complex in which the dienophile is activated for reaction with the diene. After the irreversible Diels-Alder reaction, the product has to dissociate from the Lewis-acid in order to make the catalyst available for another cycle. The overall... 

Under acidic conditions, furfuryl alcohol polymerizes to black polymers, which eventually become crosslinked and insoluble in the reaction medium. The reaction can be very violent and extreme care must be taken when furfuryl alcohol is mixed with any strong Lewis acid or Brn nstad acid. Copolymer resins are formed with phenoHc compounds, formaldehyde and/or other aldehydes. In dilute aqueous acid, the predominant reaction is a ring opening hydrolysis to form levulinic acid [123-76-2] (52). In acidic alcohoHc media, levulinic esters are formed. The mechanism for this unusual reaction in which the hydroxymethyl group of furfuryl alcohol is converted to the terminal methyl group of levulinic acid has recendy been elucidated (53). 

Stabilization Mechanism. Zinc and cadmium salts react with defect sites on PVC to displace the labHe chloride atoms (32). This reaction ultimately leads to the formation of the respective chloride salts which can be very damaging to the polymer. The role of the calcium and/or barium carboxylate is to react with the newly formed zinc—chlorine or cadmium—chlorine bonds by exchanging ligands (33). In effect, this regenerates the active zinc or cadmium stabilizer and delays the formation of significant concentrations of strong Lewis acids. 

Lactams can also be polymerized under anhydrous conditions by a cationic mechanism initiated by strong protic acids, their salts, and Lewis acids, as weU as amines and ammonia (51—53). The complete reaction mechanism is complex and this approach has not as yet been used successfully in a commercial process. 

Addition Chlorination. Chlorination of olefins such as ethylene, by the addition of chlorine, is a commercially important process and can be carried out either as a catalytic vapor- or Hquid-phase process (16). The reaction is influenced by light, the walls of the reactor vessel, and inhibitors such as oxygen, and proceeds by a radical-chain mechanism. Ionic addition mechanisms can be maximized and accelerated by the use of a Lewis acid such as ferric chloride, aluminum chloride, antimony pentachloride, or cupric chloride. A typical commercial process for the preparation of 1,2-dichloroethane is the chlorination of ethylene at 40—50°C in the presence of ferric chloride (17). The introduction of 5% air to the chlorine feed prevents unwanted substitution chlorination of the 1,2-dichloroethane to generate by-product l,l,2-trichloroethane. The addition of chlorine to tetrachloroethylene using photochemical conditions has been investigated (18). This chlorination, which is strongly inhibited by oxygen, probably proceeds by a radical-chain mechanism as shown in equations 9—13. 

The most important reaction with Lewis acids such as boron trifluoride etherate is polymerization (Scheme 30) (72MI50601). Other Lewis acids have been used SnCL, Bu 2A1C1, Bu sAl, Et2Zn, SO3, PFs, TiCU, AICI3, Pd(II) and Pt(II) salts. Trialkylaluminum, dialkylzinc and other alkyl metal initiators may partially hydrolyze to catalyze the polymerization by an anionic mechanism rather than the cationic one illustrated in Scheme 30. Cyclic dimers and trimers are often products of cationic polymerization reactions, and desulfurization of the monomer may occur. Polymerization of optically active thiiranes yields optically active polymers (75MI50600). 

Most other studies have indicated considerably more complex behavior. The rate data for reaction of 3-methyl-l-phenylbutanone with 5-butyllithium or n-butyllithium in cyclohexane can be fit to a mechanism involving product formation both through a complex of the ketone with alkyllithium aggregate and by reaction with dissociated alkyllithium. Evidence for the initial formation of a complex can be observed in the form of a shift in the carbonyl absorption band in the IR spectrum. Complex formation presumably involves a Lewis acid-Lewis base interaction between the carbonyl oxygen and lithium ions in the alkyllithium cluster. 

A large number of Brpnsted and Lewis acid catalysts have been employed in the Fischer indole synthesis. Only a few have been found to be sufficiently useful for general use. It is worth noting that some Fischer indolizations are unsuccessful simply due to the sensitivity of the reaction intermediates or products under acidic conditions. In many such cases the thermal indolization process may be of use if the reaction intermediates or products are thermally stable (vide infra). If the products (intermediates) are labile to either thermal or acidic conditions, the use of pyridine chloride in pyridine or biphasic conditions are employed. The general mechanism for the acid catalyzed reaction is believed to be facilitated by the equilibrium between the aryl-hydrazone 13 (R = FF or Lewis acid) and the ene-hydrazine tautomer 14, presumably stabilizing the latter intermediate 14 by either protonation or complex formation (i.e. Lewis acid) at the more basic nitrogen atom (i.e. the 2-nitrogen atom in the arylhydrazone) is important. 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

Since the revised Biginelli mechanism was reported in 1997, numerous papers have appeared addressing improvements and variations of this reaction. The improvements include Lewis acid catalysis, protic acid catalysis, non-catalytic conditions, and heterogeneous catalysis. In addition, microwave irradiation (MWI) has been exploited to increase the reaction rates and yields. 

In all the reactions described so far a chiral Lewis acid has been employed to promote the Diels-Alder reaction, but recently a completely different methodology for the asymmetric Diels-Alder reaction has been published. MacMillan and coworkers reported that the chiral secondary amine 40 catalyzes the Diels-Alder reaction between a,/ -unsaturated aldehydes and a variety of dienes [59]. The reaction mechanism is shown in Scheme 1.73. An a,/ -unsaturated aldehyde reacts with the chiral amine 40 to give an iminium ion that is sufficiently activated to engage a diene reaction partner. Diels-Alder reaction leads to a new iminium ion, which upon hydrolysis af-... 

This study suggests a radically new explanation for the nature of Lewis acid activation in the Simmons-Smith cyclopropanation. The five-centered migration of the halide ion from the chloromethylzinc group to zinc chloride as shown in TS2 and TS4 has never been considered in the discussion of a mechanism for this reaction. It remains to be seen if some experimental support can be found for this unconventional hypothesis. The small energy differences between all these competing transition states demand caution in declaring any concrete conclusions. 

There have been few mechanistic studies of Lewis acid-catalyzed cycloaddition reactions with carbonyl compounds. Danishefsky et ah, for example, concluded that the reaction of benzaldehyde 1 with trans-l-methoxy-3-(trimethylsilyloxy)-l,3-di-methyl-1,3-butadiene (Danishefsky s diene) 2 in the presence of BF3 as the catalyst proceeds via a stepwise mechanism, whereas a concerted reaction occurs when ZnCl2 or lanthanides are used as catalysts (Scheme 4.3) [7]. The evidence of a change in the diastereochemistry of the reaction is that trans-3 is the major cycloaddition product in the Bp3-catalyzed reaction, whereas cis-3 is the major product in, for example, the ZnCl2-catalyzed reaction - the latter resulting from exo addition (Scheme 4.3). 

The mechanism of the reaction of ethyl glyoxylate 4 with 2,3-dimethyl-l,3-hutadiene 5 leading to the ene product 7 is shown in Scheme 4.5. This brief introduction to the reaction mechanism for cycloaddition reactions of carhonyl compounds activated hy Lewis acids indicates that many factors influence the course of the reaction. 

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],... 

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