Diels Chiral Lewis acid catalyzed

The Chiral Lewis Acid-catalyzed Diels-AIder Reaction... 

The Chiral Lewis Acid-catalyzed Diels-Alder Reaction 9 Fig. 1.1 CAB catalyst 3 and methacrolein Me... 

Base catalyzed Diels- Chiral Lewis acids (see ... 

S. Otto, G. Boccaletti, J. B. F. N. Engberts, A Chiral Lewis-Acid-Catalyzed Diels-Alder Reaction. Water-Enhanced Enantioselectivity J. Am. Chem. Soc 1998, 120, 4238-4239. 

The most important development within the field of Diels-Alder chemistry during the past two decades must be considered to be the design and application of chiral Lewis acid catalysts. From the mid 80s on, the number of literature reports about the design and application of chiral Lewis acids in the synthesis of chiral Diels-Alder adducts from achiral precursors grew exponentially, but it started to level off and decrease again in the mid 90s. Several excellent reviews about the application of chiral Lewis acids in Diels-Alder reactions have been published41,43 44. In this section, the recent literature about the chiral Lewis acid catalyzed all-carbon Diels-Alder reactions of dienes with dienophiles is reviewed, which, as such, has not been reviewed before. 

The chiral Lewis acid catalyzed cycloaddition of methacrolein 310 to cyclopentadiene predominantly affording exo cycloadduct 322 together with some 323 has been extensively investigated. The application of menthoxyaluminum dichloride (324) as the chiral catalyst in this reaction represents one of the earliest examples of a chiral Lewis acid catalyzed Diels-Alder reaction206 (equation 90). The authors confirmed their results in 1987, but the ee was revised from 72% to 57%207. 

The critical step in the enantioselective and stereocontrolled total synthesis of eunicenone A by E.J. Corey et al. was the highly efficient chiral Lewis acid catalyzed intermolecular Diels-Alder cycloaddition reaction The diene component was mixed with 5 equivalents of 2-bromoacrolein and 0.5 equivalents of the chiral oxazaborolidine catalyst in CH2CI2 at -78 °C for 48h. The reaction gave 80% of the desired cycloadduct in 97% ee and the endolexo selectivity was 98 2. 

Table 3. Chiral Lewis acid-catalyzed asymmetric hetero-Diels-Alder reactions of enones with vinyl ethers 26a-c...

Early applications of chiral Lewis acid catalyzed stereoselective Diels Alder reactions used either boron- or aluminum-derived systems in carbocyclic ring formation18 1Q, or studied the effect of chiral shift reagents, such as Eu(hfc)3, in hetero-Diels-Alder cycloadditions of carbonyl compounds to dienes20 23,77, 78. The latter type of transition metal catalyzed addition is classified as heterocarboration and is described in Section 1.5.8.4. 

Catalytic asymmetric Diels-Alder reactions are presented by Hayashi, who takes as the starting point the synthetically useful breakthrough in 1979 by Koga et al. The various chiral Lewis acids which can catalyze the reaction of different dieno-philes are presented. Closely related to the Diels-Alder reaction is the [3-1-2] carbo-cyclic cycloaddition of palladium trimethylenemethane with alkenes, discovered by Trost and Chan. In the second chapter Chan provides some brief background information about this class of cycloaddition reaction, but concentrates primarily on recent advances. The part of the book dealing with carbo-cycloaddition reactions is... 

Catalytic enantioselective hetero-Diels-Alder reactions are covered by the editors of the book. Chapter 4 is devoted to the development of hetero-Diels-Alder reactions of carbonyl compounds and activated carbonyl compounds catalyzed by many different chiral Lewis acids and Chapter 5 deals with the corresponding development of catalytic enantioselective aza-Diels-Alder reactions. Compared with carbo-Diels-Alder reactions, which have been known for more than a decade, the field of catalytic enantioselective hetero-Diels-Alder reactions of carbonyl compounds and imines (aza-Diels-Alder reactions) are very recent. 

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

Asymmetric Diels-Alder reactions using a dienophile containing a chiral auxiliary were developed more than 20 years ago. Although the auxiliary-based Diels-Alder reaction is still important, it has two drawbacks - additional steps are necessary, first to introduce the chiral auxiliary into the starting material, and then to remove it after the reaction. At least an equimolar amount of the chiral auxiliary is, moreover, necessary. After the discovery that Lewis acids catalyze the Diels-Alder reaction, the introduction of chirality into such catalysts has been investigated. The Diels-Alder reaction utilizing a chiral Lewis acid is truly a practical synthetic transformation, not only because the products obtained are synthetically useful, but also because a catalytic amount of the chiral component can, in theory, produce a huge amount of the chiral product. 

To overcome these problems with the first generation Brmsted acid-assisted chiral Lewis acid 7, Yamamoto and coworkers developed in 1996 a second-generation catalyst 8 containing the 3,5-bis-(trifluoromethyl)phenylboronic acid moiety [10b,d] (Scheme 1.15, 1.16, Table 1.4, 1.5). The catalyst was prepared from a chiral triol containing a chiral binaphthol moiety and 3,5-bis-(trifluoromethyl)phenylboronic acid, with removal of water. This is a practical Diels-Alder catalyst, effective in catalyzing the reaction not only of a-substituted a,/ -unsaturated aldehydes, but also of a-unsubstituted a,/ -unsaturated aldehydes. In each reaction, the adducts were formed in high yields and with excellent enantioselectivity. It also promotes the reaction with less reactive dienophiles such as crotonaldehyde. Less reactive dienes such as isoprene and cyclohexadiene can, moreover, also be successfully employed in reactions with bromoacrolein, methacrolein, and acrolein dienophiles. The chiral ligand was readily recovered (>90%). 

A great advantage of catalyst 24b compared with other chiral Lewis acids is that it tolerates the presence of ester, amine, and thioether functionalities. Dienes substituted at the 1-position by alkyl, aryl, oxygen, nitrogen, or sulfur all participate effectively in the present asymmetric Diels-Alder reaction, giving adducts in over 90% ee. The reaction of l-acetoxy-3-methylbutadiene and acryloyloxazolidinone catalyzed by copper reagent 24b, affords the cycloadduct in 98% ee. The first total synthesis of ewt-J -tetrahydrocannabinol was achieved using the functionalized cycloadduct obtained [23, 33e] (Scheme 1.39). 

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-... 

Below is a table of asymmetric Diels-Alder reactions of a,/ -unsaturated aldehydes catalyzed by chiral Lewis acids 1-17 (Fig. 1.10, 1.11). The amount of catalyst, reaction conditions (temperature, time), chemical yield, endojexo selectivity, and optical purity are listed (Table 1.32). 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

The use of catalysts for a Diels-Alder reaction is often not necessary, since in many cases the product is obtained in high yield in a reasonable reaction time. In order to increase the regioselectivity and stereoselectivity (e.g. to obtain a particular endo- or exo-product), Lewis acids as catalysts (e.g. TiCU, AICI3, BF3-etherate) have been successfully employed." The usefulness of strong Lewis acids as catalysts may however be limited, because they may also catalyze polymerization reactions of the reactants. Chiral Lewis acid catalysts are used for catalytic enantioselective Diels-Alder reactions. ... 

A new chiral ligand for the Fe-Lewis-acid catalyzed asymmetric Diels-Alder reaction [117]... 

Hiroi K. Transition Metal or Lewis Acid-Catalyzed Asymmetric Reactions With Chiral Organosulfur Eunctionahty Rev. Heteroat. Chem. 1996 14 21-57 Keywords hefero-Diels-Alder reactions, asymmetric synthesis, chiral organosulfur functionality... 

Zeijden [112] used chiral M-functionalized cyclopentadiene ligands to prepare a series of transition metal complexes. The zirconium derivative (82 in Scheme 46), as a moderate Lewis acid, catalyzed the Diels-Alder reaction between methacroleine and cyclopentadiene, with 72% de but no measurable enantiomeric excess. Nakagawa [113] reported l,T-(2,2 -bis-acylamino)binaphthalene (83 in Scheme 46) to be effective in the ytterbium-catalyzed asymmetric Diels-Alder reaction between cyclopentadiene and crotonyl-l,3-oxazolidin-2-one. The adduct was obtained with high yield and enantioselectivity (97% yield, endo/exo = 91/9, > 98% ee for the endo adduct). The addition of diisopropylethylamine was necessary to afford high enantioselectivities, since without this additive, the product was essentially... 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

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