Lewis acidity, and Brpnsted

For our microwave-promoted high-throughput library synthesis we decided to use a protocol that utilizes a combination of Lewis acids and Brpnsted acids as catalysts. 

Although the development of a variety of Lewis acids has enabled the reahzation of a wide range of catalytic asymmetric reactions, most of the catalysts have limited activity in terms of either enantioselectivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activates only one side of the substrate in an intermolecular reaction, whereas the latter not only can activate both sides of the substrate but also can control the orientation of the substrate. If this kind of synergistic cooperation could be realized in synthetic asymmetric catalysis, it would open up a new field in asymmetric synthesis, and a wide range of applications might well ensure. In this section we discuss asymmetric two-center catalysis promoted by chiral lanthanide complexes with Lewis acidity and Brpnsted basicity [44,45]. 

Asymmetric Michael addition of a-cyanoacetates to enones, constructing densely adjacent quaternary and tertiary stereocentres, has been attained by combination of a catalytic action of soft Pd complexes as soft Lewis acids and Brpnsted acids, for example, AcOH. Investigation of the kinetics revealed that the C-C-bond-forming step takes place almost instantaneously with the bis-palladium complex right after the substrate coordination. ... 

The use of lanthanide complexes in asymmetric catalysis was pioneered by Danishefsky s group with the hetero-Diels-Alder reaction,and their utility as chiral Lewis acid catalysts was shown by Kobayashi. The Brpnsted base character of lanthanide-alkoxides has been used by Shibasaki for aldol reactions, cyanosilylation of aldehydes and nitroaldol reactions.The combination of Lewis acid and Brpnsted base properties of lanthanide complexes has been exploited in particular by Shibasaki for bifunctional asymmetric catalysis. These bimetallic lanthanide-main-group BINOL complexes are synthesized according to the following routes ... 

SCHEME 2.6 Monomer reactivity for a series of common monomers which will polymerize with Lewis acids and Brpnsted acids. Scheme adapted from Matyjaszewski K, Cationic Polymerizations Mechanisms, Synthesis, and Applications. New York Marcel Dekker 1996. 1996 Marcel Dekker, New York. 

Class II aldolase mimics (Scheme 10.4) were the first small-molecule catalysts that were reported for the direct intermolecular aldol reaction. These catalysts are characterized as bimetallic complexes that contain both Lewis acidic and Brpnsted basic sites. Shibasaki et al. first reported on the use of such a catalyst in the aldol reaction in 1997, demonstrating its potential with the reaction of various acetophenones 52 and aldehydes 53 (Scheme 10.13). Aldols 55 were obtained in good yields and enantioselectivities. A similar approach was used in the direct catalytic asymmetric aldol-Tishchenko reaction.Nevertheless, for the moment, this method does not provide access to true polypropionate fragments. ... 

Direct intermolecular aldol reaction leading to polypropionate building blocks was achieved by Mahrwald in 2(X)0. Also in this case the promoting system contains both, Lewis acidic and Brpnsted basic sites, and is used in stoichiometric amounts (Scheme 10.14). It is interesting to note that the best results were obtained when racemic BINOL-Ti(Oi-Bu)2 59 was combined with enantiomeri-cally pure (/f)-mandelic acid 60. 

Brpnsted acids have shown good-to-excellent levels of selectivity in C S bond formations. This chapter aims to review the stereoselectivity aspect of C—S bond formations that use commodity chemicals such as alkynes, alkenes, and alkanes. The stereoselective functionalization of alkynes is reviewed in section 1 using hydrothiolation, bisthiolation, and carbothiolation that necessitate transition metal and Brpnsted acid catalysis. The next section covers sulfethera-tion and conjugate addition reactions, where electron-rich and electron-poor alkenes are exploited under Lewis acid and Brpnsted acid catalysis. The last section is centered on the use of alkanes in the stereoselective 5-alkylation catalyzed by transition metal and organocatalysis. 

The carboranyl alcohol can also be prepared from the stannyl carborane and an aldehyde using Pd2(dba)3-CHCl3/dppe. The carborane is stable to Brpnsted and Lewis acids and to LiAlH.. 

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. 

The hydrogen ion accepts the lone pair of electrons from the ammonia to form the ammonium ion. The hydrogen ion, because it accepts a pair of electrons, is the Lewis acid. The ammonia, because it donates a pair of electrons, is the Lewis base. This reaction is also a Brpnsted-Lowry acid-base reaction. This illustrates that a substance may be an acid or a base by more than one definition. All Brpnsted-Lowry acids are Lewis acids, and all Brpnsted-Lowry bases are Lewis bases. However, the reverse is not necessarily true. 

This review will concentrate on metal-free Lewis acids, which incorporate a Lewis acidic cation or a hypervalent center. Lewis acids are considered to be species with a vacant orbital [6,7]. Nevertheless, there are two successful classes of organocatalysts, which may be referred to as Lewis acids and are presented in other chapter. The first type is the proton of a Brpnsted acid catalyst, which is the simplest Lewis acid. The enantioselectivities obtained are due to the formation of a chiral ion pair. The other type are hydrogen bond activating organocatalysts, which can be considered to be Lewis acids or pseudo-Lewis acids. 

The Beckmann rearrangement of oxime esters is catalysed by Brpnsted or Lewis acids and these conversions are usually non-stereospecific, as demonstrated by the studies of Beckmann rearrangement of 1-indanone oximes derivatives 240a with aluminium chloride as a catalyst " (equation 88). 

Distinguish Lewis acids and bases from Brpnsted-Lowry acids and bases. Give an example of each. 

Other nucleophiles such as nitromethane can also be used for this reaction. Thus, by the catalysis of (fl)-LPB (LaK3tris((/ )-binaphthoxide) (20 mol %), in which La works as a Lewis acid and K-naphthoxide works as a Brpnsted base, nitromethane reacted with chalcone to give the Michael adduct in 85% yield and 93% ee (Scheme 8D.8) [22], Addition of BuOH (120 mol %) gave a beneficial effect on the reactivity as well as the enantioselectivity of this reaction. 

There are thus two classes of acids on surfaces of metal oxides Lewis acids and Brdnsted acids (which are also termed proton acids). The weight of evidence (1-8) shows that strong Brpnsted acids are the primary seat of catalytic activity for skeletal transformations of hydrocarbons. In the solids under review, they consist of protons associated with surface anions. 

Pure activated aluminas are also capable of catalyzing the skeletal isomerization of olefins (104, 105), but at considerably higher temperatures (350°-400°C) than those required for double-bond isomerization. The results obtained by Pines and Haag (105,106) leave little doubt that this type of isomerization is acid catalyzed. They found that (a) skeletal isomerization of cyclohexane or 3,3-dimethylbutene-l over pure alumina was poisoned upon ammonia addition and (b) the order of appearance of products from 3,3-dimethylbutene-l isomerization as contact time is increased was that predicted from carbonium ion theory. They also used indicator tests to show that the seat of acid activity in -y-alumina consists of Lewis, not Br0nsted, acidity. Independent infrared studies of pyridine chemisorbed on pure alumina have verified the existence of Lewis acidity and the absence of Brpnsted acidity in pure alumina (23, 107). 

Of course, in a generalized way, the proton H+ is also a Lewis acid and the Brpnsted acids and bases also fall into the Lewis categories. 

As discussed, superacids, similar to conventional acid systems, include both Brpnsted and Lewis acids and their conjugate systems. Protic (Brpnsted-type) superacids include strong parent acids and the mixtures thereof, whose acidity can be further enhanced by various combinations with Lewis acids (conjugate acids). The following are the most frequently used superacids. 

A quantitative method to determine the strength of Lewis acids and to establish similar scales as discussed in the case of Brpnsted acids would be very useful. However, establishing such a scale is extremely difficult and challenging. Whereas the Brpnsted acid-base interaction always involves proton transfer, which allows a meaningful quantitative comparison, no such common relationship exists in the Lewis acid-base interaction. The result is that the definition of strength has no real meaning with Lewis acids. 

According to the hypothetical catalytic cycle (Figure 36), the lanthanum atom is believed to function as a Lewis acid and a lithium binaphthoxide moiety as a Brpnsted base. The nature of the coordination of the aldehyde appears to be of first importance. This coordination provides activation of the aldehyde for reaction with the hypothetical LLB-enolate (II) (which on the basis of pKa values can be present at most in low concentration), and also controls of the orientation of the aldehyde for enantioselective reaction. A H NMR study also supports the existence of the coordination between aldehydes and the lanthanum cation.89... 

Reactions (a) and (c) are reactions between Brpnsted-Lowry acids and bases the stronger acid and stronger base are identified. Reactions (b) and (d) occur between Lewis acids and bases. 

As in general chemistry, acid-base reactions are of fundamental importance in organic chemistry. Organic acids and bases, as well as inorganic acids and bases, occur frequently in reactions, and large numbers of reactions are catalyzed by Brpnsted acids and bases and Lewis acids and bases. 

For example, draw the Lewis acid-base reaction between eyelohexene and H-Cl. The Brpnsted-Lowiy acid HCI is also a Lewis acid, and cyclohexene, having a n bond, is the Lewis base. 

A mechanism for this reaction has been proposed and is summarized in Sch. 10. The catalyst 64 is thought to be bifunctional with the aluminum center operating as a Lewis acid and the lithium naphthoxide operating as a Lowry-Brpnsted base. It was envisaged that the aldehyde coordinates with the aluminum to give the complex 69 and deprotonation of the dimethyl phosphite then gives the aggregate 70 in which the phosphite anion is positioned for P-alkylation of the aldehyde that will occur selectively from the si face when the catalyst is prepared from (f )-BINOL. 

The surface of alumina is covered by five distinct types of surface hydroxyls in their coordination to the aluminum. The total hydroxyl groups of the y-alumn-ina is about 3 /imol/m. Upon heating to temperatures above 200°C, there is a consequent loss of these surface hydroxyls. Even though there is a loss of surface hydroxyls that may participate as weak Brpnsted sites, the activity of the alumina increases with increase of hydroxyl loss, because they are converted into Lewis acidic and basic sites which may act as stronger adsorption sites. The activity of the five types of hydroxyl sites on the alumina is dependent on the amount of water present on the surface. Furthermore, the highest surface activity would be obtained with lesser amounts of physically sorbed water. The presence of Na20, a common impurity of the y-alumina, is known to affect the pH of the y-alumnina to a more basic alumina [3],... 

Zirconia and titania both contain Lewis-acid and Lewis-base sites, with the latter having stronger adsorption properties. The titania phase also has strong Brpnsted acidic sites. Basic compounds are less retained on zirconia and titania phases, due to their basic nature. Neutral compounds such as poly aromatic hydrocarbons (PAH), due to their rr-electron system, behave as Lewis bases and the interactions with Lewis acid sites on the zirconia and titania packing materials become dominant for retention. 

---