Lewis acid Subject

The most dramatic observation in Figure 4.4 is the reduction in the energy of the cr orbitals, the LUMO, in the series. As a consequence, the oxy and halo compounds are strong Lewis acids (subject to nucleophilic attack) and strong oxidizing agents (can readily accept electrons). 

In order to be able to provide answers to these questions, a Diels-Alder reaction is required that is subject to Lewis-acid catalysis in aqueous media. Finding such a reaction was not an easy task. Fortunately the literature on other Lewis-acid catalysed organic reactions in water was helpful to some extent... 

Finally, if there could be a way in which in water selective ri Jt-coordination to the carbonyl group of an a,P-imsatLirated ketone can be achieved, this would be a breakthrough, since it would subject monodentate reactants to catalysis by hard Lewis acids ". ... 

The parameters and Ca are associated with the Lewis acid, and Eg and Cb with the base. a and b are interpreted as measures of electrostatic interaction, and Ca and Cb as measures of covalent interaction. Drago has criticized the DN approach as being based upon a single model process, and this objection applies also to the — A/y fBFs) model. Drago s criticism is correct, yet we should be careful not to reject a simple concept provided its limits are appreciated. Indeed, many very useful chemical quantities are subject to this criticism for example, p o values are measures of acid strength with reference to the base water. 

The mechanism of the carbo-Diels-Alder reaction has been a subject of controversy with respect to synchronicity or asynchronicity. With acrolein as the dieno-phile complexed to a Lewis acid, one would not expect a synchronous reaction. The C1-C6 and C4—C5 bond lengths in the NC-transition-state structure for the BF3-catalyzed reaction of acrolein with butadiene are calculated to be 2.96 A and 1.932 A, respectively [6]. The asynchronicity of the BF3-catalyzed carbo-Diels-Alder reaction is also apparent from the pyramidalization of the reacting centers C4 and C5 of NC (the short C-C bond) is pyramidalized by 11°, while Cl and C6 (the long C-C bond) are nearly planar. The lowest energy transition-state structure (NC) has the most pronounced asynchronicity, while the highest energy transition-state structure (XT) is more synchronous. 

This area of reactivity has been the subject of excellent reviews (J5). Silyl enol ethers are not sufficiently nucleophilic to react spontaneously with carbonyl compounds they do so under the influence of either Lewis acids or fluoride ion, as detailed above. Few clear trends have emerged from the somewhat limited number of definitive studies reported so far, with ambiguities in diastereoisomeric assignments occasionally complicating the issue even further. 

Among the unique features of Sc(03SCF3)3 is its ability to function as a catalyst in hydroxylic solvents. Other dienophiles, including (V-acryloyloxazolidinones, also are subject to catalysis by Sc(03SCF3)3. Indium trichloride is another Lewis acid that can act as a catalyst in aqueous solution.40... 

A valine-derived oxazaborolidine derivative has been found to be subject to activation by Lewis acids, with SnCl4 being particularly effective.98 This catalyst combination also has reduced sensitivity to water and other Lewis bases. 

Conjugate addition to acyclic enones is subject to chelation control when TiCl4 is used as the Lewis acid. Thus, whereas the A-enone 12 gives syn product 13 via an acyclic TS, the Z-isomer 14 reacts through a chelated TS to give 15.133... 

When an aldehyde subject to chelation control is used, the syn stereoisomer dominates, with MgBr2 as the Lewis acid.164... 

P-Hydroxyketones are also subject to fragmentation. Lewis acids promote fragmentation of mixed aldol products derived from aromatic aldehydes.100... 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

Under Lewis-acid-catalyzed conditions, electron-rich arenes can be added to alkenes to generate Friedel-Crafts reaction products. This subject will be discussed in detail in Chapter 7, on aromatic compounds. However, it is interesting to note that direct arylation of styrene with benzene in aqueous CF3CO2H containing H2PtCl6 yielded 30-5% zram-PhCH CHR via the intermediate PhPt(H20)Cl4.157 Hydropheny-lation of olefins can be catalyzed by an Ir(III) complex.158... 

Recently, water-tolerating Lewis acid has been used to catalyze various Diels-Alder reactions in aqueous media. An important aspect of the Diels-Alder reaction is the use of Lewis acids for the activation of the substrates. While most Lewis acids are decomposed or deactivated in water, Bosnich reported that [Ti(Cp )2(H20)2]2+ is an air-stable, water-tolerant Diels-Alder catalyst.35 A variety of different substrates were subjected to the conditions to give high yields and selectivity (Eq. 12.6). 

The design and application of chiral, non-racemic Lewis acids for the asymmetric Diels-Alder reaction has recently been a subject of considerable interest.9 Several methods have been developed in many laboratories1 2 3 4 5 6 7 10 but catalysts are still needed that are more efficient in governing the stereochemical course of the cycloaddition reaction. 

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.,... 

Like so many other reactions, the ene reaction has been given new life by metal catalysis. The use of metals ranges from common Lewis acids, which simply lower the barrier of activation of the hetero-ene reactions to transition metal catalysts which are directly involved in the bond-breaking and -forming events, rendering reactions formal ene processes. This review is meant to serve as a guide to the vast amount of data that have accumulated in this area over the past decade (1994-2004). If a particular subject has been reviewed recently, the citation is provided and only work done since the time of that review is included here. Finally, the examples included within are meant to capture the essence of the field, the scope, limitations, and synthetic utility therefore, this review is not exhaustive. 

The [4 + 3]-cycloaddition is a commonly used method for the synthesis of seven-membered rings.9 Many of these reactions involve metals, principally in the role of a Lewis acid as exemplified in Equation (10). These Lewis acid-catalyzed [4 + 3]-cycloadditions have been reviewed by Rigby,62 Sarhan,63 Harmata,64,65 and Hoffmann,66 and will not be reviewed here due to the role of the metal as a Lewis acid. Several computational papers on this subject have also been published.67-71... 

The addition of an enolsilane to an aldehyde, commonly referred to as the Mukaiyama aldol reaction, is readily promoted by Lewis acids and has been the subject of intense interest in the field of chiral Lewis acid catalysis. Copper-based Lewis acids have been applied to this process in an attempt to generate polyacetate and polypropionate synthons for natural product synthesis. Although the considerable Lewis acidity of many of these complexes is more than sufficient to activate a broad range of aldehydes, high selectivities have been observed predominantly with substrates capable of two-point coordination to the metal. Of these, benzy-loxyacetaldehyde and pyruvate esters have been most successful. 

All attempts to. substitute trigonalplanar boranes for moderately strong Lewis acids having tetrahedral or trigonalbipyramidal configurations in the acid-assisted F vs. R substitution in XeF2 have failed thus far. Consequently, the reaction of XeF2 with boranes will be the subject of discussion here. 

The incorporation of comonomers into PET and other polyesters, with the intent that these comonomers would then serve as the site for additional, postpolymerization reactions, has not been widely explored. A potential difficulty in such an approach is that the reactive comonomer cannot react under PET synthesis conditions of ca. 285 °C/2h/Lewis acid catalyst if the modification is to be effective. Two such systems, stable under PET synthesis, and then subjected to post-polymerization reactions, have been recently reported. 

The nitrido and phosphido complexes of TMs have been the subjects of intensive experimental studies in the recent years. Of particular interest has been the issue of Lewis basicity of the nitrogen and phosphorus atoms in the TM=N and TM=P groups. Table 7.17 lists the BDEs calculated at the MP2/II, B3LYP/B and CCSD(T)/B levels of theory for LnMN-X and LnMP-X, where X is a group-13 Lewis acid or a chalcogen atom [86, 87]. 

Another total synthesis of elisapterosin B (27), as well as colombiasin A (36) was reported by the Rychnovsky group [39]. The underlying concept of this approach was the proposed biosynthetic pathway shown in Scheme 8. Thus, the authors decided to prepare the putative metabolite 46 in 0-methylated form 128 and subject it to Lewis acid conditions in the hope that cyclization might occur to either 27 or 36, or both. The required precursor 128 would stem from an intermolecular Diels-Alder reaction between diene 129 and quinone 130 (Scheme 20). 

The nature of the acidic sites is still subject of lively discussion. One school of thought, based on a proposition by Thomas (348), attributes the acidity to substitution of AP+ ions for Si + ions in a tetrahedrally linked silica network. Electroneutrality is obtained by addition of protons. Others think that Lewis acid sites, as proposed by Milliken et al. (349), are responsible for the catalytic activity, Gray (350) suggested that only the alumina content was responsible and that a spinel-like phase was formed on heating with protons on certain octahedral positions. 

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