Lewis acids chiral catalysis

In this chapter Lewis-acid-mediated reactions have been summarized. While more than stoichiometric amounts of the Lewis acids were employed in conventional reactions, many efforts have been made to reduce the amounts of Lewis acid needed, and many truly catalytic reactions have been developed. Chiral Lewis-acid catalysis has been of great interest in the 1990s and early 2000s, and various combinations of metals and ligands have been investigated. Importantly, the established understanding that Lewis acids are easily hydrolyzed in water has been exploded. Water-compatible Lewis acids are stable in air and moisture, and are easily recovered and reused in many cases. These Lewis acids may solve recent environmental issues, and will be used further in many reactions in future. 

S. Kobayashi, S. Nagayama, T. Busujima, Chiral Lewis Acid Catalysis in Aqueous Media. Catalytic Asymmdric Aldol Readions of Silyl Enol Ethers with Aldehydes in a Protic Solvent Induding Water Chem. Lett. 1999, 71-72. 

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. 

Nugent, W. A. (1992) Chiral Lewis acid catalysis Enantioselective addition of azide to meso-epoxides., J. Am. Chem. Soc, 114 2768-2769. 

Due to increasing demands for optically active compounds, many catalytic asymmetric reactions have been investigated in this decade. However, asymmetric catalysis in water or water/organic solvent systems is difficult because many chiral catalysts are not stable in the presence of water [19]. In particular, chiral Lewis acid catalysis in aqueous media is extremely difficult because most chiral Lewis acids decompose rapidly in the presence of water [20, 21]. To address this issue, catalytic asymmetric reactions using water-compatible Lewis acids with chiral ligands have been developed [22-29]. 

The first examples of chiral Lewis acid catalysis in the opening of diactivated cyclopropane derivatives (224) with nitrones (225) has been demonstrated, giving rise to the tetrahydro-l,2-oxazines (226). High enantioselectivities (71-96% ee) were attained with Ni(C104)2 and Ph-DBFOX ligand (227).262... 

Chiral Lewis Acid Catalysis of the Diels-Alder Reaction. 12... 

Asymmetric Alder-Ene reactions have been accomplished using optically-enriched starting materials, chiral auxiliaries, and chiral catalysts. The use of chiral catalysts has been applied to both chiral Lewis acid catalysis and asymmetric catalysis with chiral ligands. Some of these examples have already been cited for example, the use of a chiral auxiliary or optically-enriched substrates to generate optically-enriched products (LA catalysis with chiral auxiliary 30 + 31 -+ 32 or with optically-enriched starting materials 75 or 77 — 76 or 78, respectively or chiral LA applied to desymmetrization 33 + 34 — 35). More recent examples are displayed here, in particular, the use of chiral catalysts. 

Chiral Lewis acid catalysis in aqueous media is known to be very difficult to attain, because most chiral Lewis acids are not stable in the presence of water, even using water-compatible Lewis acids. A breakthrough in this field has been reported in catalytic asymmetric hydroxymethylation in aqueous media [170]. It was found that a combination of Sc(OTf)3 and ligand (3) worked effectively in the reaction of a commercially available formaldehyde water solution with several types of silyl enol ethers (Scheme 12.74) [171]. 

The enantioselective Diels-Alder reaction is another main motif in chiral Lewis acid catalysis. In 1996, Itsuno and coworkers reported an asymmetric Diels-Alder reaction using polymer-supported catalysts under flow conditions. Immobilized chiral oxazoboloridune (34) was prepared from a copolymer of N-sulfonylvabne and borane having styrene moiety, affording the Diels-Alder adduct in an enantioselective manner (up to 71% yield) [126], The authors used a gravity-fed-type column for the flow reaction. Ti-TADDOL-functionalized monolithic resins (35) were developed by Altava and Luis for the asymmetric Diels-Alder reaction (Scheme 7.30). 

In coordination with the bulky Lewis acid, the carbonyl group is expected to be partially rehybridized to generate catioiuc species before the nucleophilic alkylation process. This late transition state of the reaction is very different from the early transition state, which is popular for most of the alkylation of carbonyl compounds. Thus, the stereochemical outcomes of these reactions could be the opposite of what we observed in normal small Lewis acid (Li)/nucleophilic alkylation processes. These observations provide us a critical guideline with which to challenge the carbonyl activation for asymmetric alkylation based on chiral Lewis acid catalysis (Scheme 6). 

At this point, one can see the impact of the chiral Lewis acid catalysis in the indirect small-molecule-catalyzed asymmetric aldol reactions. More examples together with exhaustive discussions about the stereochemical... 

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