Subject Lewis acid activation

It is widely accepted that the carbonyl reactivity toward nucleophiles increases in the order aldehyde>ketone>ester>amide [6]. This reactivity order is simply based on the extent to which each carbonyl carbon is sterically and electronically activated. However, reactivities might change when these carbonyl substrates are subjected to a Lewis acid. It is generally assumed that the coordination capability of the carbonyl oxygen to Lewis acids is the means by which Lewis acids activate carbonyl substrates. Thus, in some re.spects, the reaction rate parallels the Lewis basicity of the carbonyls. Furthermore, the reactivity of a carbonyl substrate depends on the reaction type as well as the Lewis acid employed. Special care must be taken in assessing the relationship between the relative reaction rate, the relative Lewis basicity, and the inherent carbonyl reactivity of each substrate. It is instructive to take a look at the following example (Schemes 2-2 and 2-3 Fig. 2-1). 

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. 

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). 

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 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. 

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. 

Metal ions are Lewis acids and as such catalyze many reactions which are also subject to specific acid catalysis by the proton. Reactions in which metal ions are involved are often best described as metal ion-promoted reactions as the products of the reaction often remain bound to the metal ion. Although scattered references to metal ion-promoted reactions are to be found in the early literature it was not until the late 1950s that such reactions began to be studied in detail. A strong driving force has been the realization that some 30% of enzymes are metalloenzy-mes or require metal ions for activity. Many of the reactions dealt with in this article have been studied in an attempt to delineate possible mechanisms for enzymic processes. 

The subject of acidity is viewed broadly, and examples are not restricted to IEs on protonation reactions. Among the generalizations are IEs on Lewis acidity and basicity, IEs on conformational and tautomeric equilibria that can be converted into IEs on acidity, and IEs in chromatographic separations that depend on IEs on acidity. IEs on enzyme-catalyzed reactions are omitted, because their emphasis is ordinarily on kinetic IEs, which are used to determine mechanisms.4 However, it should be recognized that equilibrium IEs are operative in the association of substrates with enzyme active sites.5,6... 

Glycosyl imines are not very reactive dienophiles in [4 + 2] cycloaddition reactions. However, they can be subjected to cycloaddition reactions after activation with Lewis acids [51]. TV-Galactosyl imines 7 were shown to react with isoprene in the presence of zinc(II) chloride to give the corresponding 4-methyl piperidine derivatives 43 (Scheme 25). 

Neutral organoaluminum(m) compounds have broad applicability in organic synthesis as extremely strong Lewis-acidic reaction promoters. However, the exploration of increased reactivity in aluminum is a key subject for expanding their utility, especially in polymer synthesis and in the activation of relatively stable substrates... 

It therefore seems quite natural to choose silica, silica aluminas, and aluminium oxide as the objects of the first systematical quantum-chemical calculations. These compounds do not contain transition elements. They are built of the individual structural fragments primary, secondary, etc. This enables one to find the most suitable cluster models for quantum-chemical computations. The covalent nature of these structures again makes quite efficient a comparatively simple method of taking into account the boundary conditions in the cluster calculations. Finally, these systems demonstrate clearly defined Bronsted and Lewis acidity. This range of questions comprises the subject of the present review. This does not by any means imply that there are no quantum-chemical computations on the cluster models of the surface active sites of transition element oxides. It would be more proper to say that the few works of this type represent rather preliminary attempts, being far from systematic studies. Also, many of them unfortunately include some disputable points both in the statement of the problem and in the procedure of calculations. In our opinion, the situation is such that it is still unreasonable to try to summarize the results obtained, and therefore this matter is not reviewed in the present article. 

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