Enantioselective Reactions with Chiral Lewis Acids

16 Enantioselective Reactions with Chiral Lewis Acids 

Some improvements have been described for the enantioselective addition of allyltri-n-butylstannane to simple aldehydes using a catalyst prepared from BINOL and Zr(0-t Bu)4 in toluene.122 Reactions proceed 

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Chiral base catalysis was classified into five sections and reviewed. Although the reactions described herein are promoted by Bronsted or Lewis bases, the Lewis acidic characteristics of metals play important roles in both substrate activation and enantioselection. Compared with chiral Lewis acid-catalyzed reactions,... 

The first report of an asymmetric Diels-Alder reaction with chiral Lewis acids (252) was made by Russian chemists in 1976 (253). Koga was probably the first to report a meaningful enantioselective Diels-Alder reaction (Scheme 105) in which the cyclopentadiene-methacro-lein exo adduct was obtained in 72% ee with the aid of 15 mol % of a menthol-modified aluminum chloride (254). The ee is highly dependent on the structures of the substrates, and asymmetric induction has not been observed with methyl acrylate as dienophile. Disproportionation... 

The catalytic enantioselective cycloaddition reaction of carbonyl compounds with conjugated dienes has been in intensive development in recent years with the main focus on synthetic aspects the number of mechanistic studies has been limited. This chapter will focus on the development and understanding of cycloaddition reactions of carbonyl compounds with chiral Lewis acid catalysts for the preparation of optically active six-membered ring systems. 

Lewis acid catalysis is not limited to cases in which increased yields or enhanced selectivities are desired. Lewis acids offer also the possibility to induce chiral information leading to enantioselective product formation. The enantioselective induction by chiral Lewis acids found widespread application in organic synthesis, especially in the synthesis of natural products with many chiral centres. An enantioselective Diels-Alder reaction is the key step in the synthesis of an iodolactone prostaglandine precursor (Scheme 6).88... 

To accelerate aUylation with aUylstaimanes, addition of a Lewis acid is often required, because coordination of the Lewis acid to the carbonyl can enhance the electrophilicity of the substrate and facilitate the couphng reaction. Since Yamamoto showed that a nonracemic Lewis acid, chiral (acyloxy)borane (CAB), catalyzed enantioselective allylation [73], chiral Lewis acid catalysts have been extensively developed. Above all, easily available chiral compounds such as BINOL and BINAP have been most frequently used as chiral auxiliaries [74], and enantioselective allylations of C-N double bonds and of carbonyl groups have been achieved [48a, 75]. 

The asymmetric catalysis of aldol reactions with chiral Lewis bases is an important method to form C-C bonds [130-139], The emergence of Lewis base-activated Lewis acid catalysis is pioneered by the Denmark group [140-142], They used a variety of chiral phosphoramides as catalysts for the enantioselective intermolecular aldol reactions (Scheme 7,20),... 

The first example of appreciable enantioselectivity in a catalytic asymmetric Diels-Alder reaction was reported in 1979 by Koga (Equation 14) [73]. This was achieved by use of 14 mol % of an aluminum complex resulting from reaction of menthol and EtAlCl2, as formulated in the proposed catalyst structure 133. In the presence of this catalyst, cycloadduct 134 was obtained in 57 % ee and 69 % yield. This result provided an important proof of principle that catalytic enantioselective Diels-Alder reactions can indeed be achieved with chiral Lewis acids [73, 74). 

The first example of enantioselective catalysis of a Diels-Alder reaction was reported in 1979 . Since then, an extensive set of successful chiral Lewis-acid catalysts has been prepared. Some selected examples will be presented here together with their mechanistic interpretation. For a more complete... 

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. 

In 1994 Yamamoto et al. developed a novel catalyst which they termed a "Brmsted acid-assisted chiral Lewis acid" (BLA) [10] (Scheme 1.14, Table 1.3). The catalyst 7 was prepared from (R)-3,3 -dihydroxyphenyl)-2,2 -dihydroxy-l,l -binaphthyl by reaction with B(OMe)3 and removal of methanol [10a, dj. The Brmsted acid is essential for both the high reactivity of the Lewis acid and the high enantioselectivity - the... 

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%). 

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. 

Jorgensen has recently reported similar enantioselective reactions between N-tosylimines 107 and trimethylsilyldiazomethane (TMSD) catalyzed by chiral Lewis acid complexes (Scheme 1.32) [57, 53]. The cis-aziridine could be obtained in 72% ee with use of a BINAP-copper(i) catalyst, but when a bisoxazoline-copper(i) complex was used the corresponding trans isomer was fonned in 69% ee but with very poor diastereoselectivity. 

The majority of catalytic enantioselective allylation reactions involve the chiral Lewis-acid-catalysed additions of allylsilanes or allylstannanes to carbonyl compounds. Monothiobinaphthol has been used by Woodward et al. as a chiral promoter in the enantioselective catalytic allylation of aryl ketones with impure Sn(allyl)4, prepared from allyl chloride, air-oxidised magnesium and SnCl4. Therefore, the allylation of arylketones in these conditions was achieved very efficiently, since the corresponding allylic alcohols were formed in... 

Finally, the catalytic enantioselective 1,3-dipolar cycloaddition reaction has recently been developed to be a highly selective reaction of nitrones with electron-deficient alkenes activated by chiral Lewis acids. High levels of regio-, diastereo-, and enantioselectivities can now be reached using catalysts 89 <2000JOC9080>, 90 <2002JA4968>, or 91 <2005JA13386> (Scheme 29). 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

It is significant to note that this reaction is highly unusual since the prochiral element resides entirely on the nucleophile. The chiral Lewis acid exerts control of en-antiofacial selectivity by proctor through tight control of the presumed heterocycloaddition transition state, Scheme 27. In effect, extremely high fidelity is necessary to orient the 2n component with respect to the 4ji component coordinated to the chiral Lewis acid. The factors that control the diastereoselectivity in the Mukaiyama Michael reaction of crotonylimides could also control enantioselectivity in the amination reaction. That selectivities on the order of 99% ee are observed in this reaction is testament to the level of control exerted by these catalysts. 

The Diels-Alder reaction of cyclopentadiene with /3-stannylpropynal is much faster than that with /3-alkylpropy-nals, and can be made enantioselective in the presence of a chiral Lewis acid catalyst (Equation (67)).213... 

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