Chiral Lewis acids, preparation

A very simple chiral Lewis acid, prepared by mixing optically pure BINOL with 3 equiv of Me3Al, catalyzes the [4+2] cycloaddition of A-hydroxy-A-phenylacry-lamine with cyclopentadiene at 0°C in high yield (>96%) and a fairly good level of enantioselectivity (91% ee). Facile conversion of the products to the corresponding alcohols or aldehydes makes the hydroxamic acid intermediates particularly useful (Scheme 12.14). ... 

A kinetic resolution with respect to the racemic diene 66 could be achieved in the Diels-Alder reaction promoted by a chiral Lewis acid prepared from BHj in the presence of (S)-3,3 -diphenyl-l,r-binaphthalene-2,2 -diol and juglone (47) in the synthesis of (+)-emycin A and (+)-ochromycinone (35) [66] (compare previous investigations by Kelly [67]). 

A chiral Lewis acid prepared in situ from magnesium iodide and (/ ,f )-DPEN efficiently catalyzes asymmetric aza-Diels-Alder reaction of a methyl glyoxylate/p-anisidine derived imine with the Danishefsky diene to give the cyclic adduct in 97% ee (eq 11). ... 

In sharp contrast to the utility of chiral boron Lewis acids, chiral aluminum Lewis acids have been little used for asymmetric aldol reactions of silyl enolates since the first example reported by Reetz et al. [115]. Fujisawa et al. have reported that an equimolar amount of a chiral Lewis acid prepared from Et2AlCl and a bor-nane-2,3-diol promotes the aldol reaction of 48 in moderate yields with good enantioselectivity [127]. 

Acryloyl- and 3-crotonoyl-4,4-dimethyl-l,3-oxazolidin-2-ones can form a rigid complex with the Lewis acid. They react with cyclopentadiene in the presence of chiral Lewis acids, prepared in situ from ethylaluminum dichloride and chiral diols with moderate enantioselectiv-ity (36% cc)9. 

Reports of the use of chiral aluminum Lewis acids in the asymmetric aldol reaction are quite limited. The first enantioselective aluminum-catalyzed Mukaiyama aldol reaction was reported about 10 years ago (158). In this asymmetric version, /5-hydroxy ester was formed in high enantiomeric excess by the ketene silyl acetal with aldehyde in the presence of a chiral Lewis acid prepared from diethylaluminum chloride (Et2AlCl) and chiral diol derived from... 

On the other hand, a-iodolactone was found as a nice substrate to realize the practical enantioselectivity [205]. In the presence of stoichiometric amount of chiral Lewis acid prepared by the 1 1 reaction of (S,S)-(157a) and Me3Al, the quaternary carbon formation through radical allylation with allyltributyltin resulted in the... 

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... 

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%). 

Evans et al. reported that the bis(imine)-copper (II) complex 25, prepared from chiral bis(imine) ligand and Cu(OTf)2, is also an effective chiral Lewis acid catalyst [34] (Scheme 1.44, Table 1.18). By tuning the aryl imine moiety, the bis(2,6-dichlor-ophenylimine) derivative was found to be suitable. Although the endojexo selectivity for 3-alkenoyloxazolidinones is low, significant improvement is achieved with the thiazolidine-2-thione analogs, for which both dienophile reactivity and endojexo selectivity are enhanced. 

Since Evans s initial report, several chiral Lewis acids with copper as the central metal have been reported. Davies et al. and Ghosh et al. independently developed a bis(oxazoline) ligand prepared from aminoindanol, and applied the copper complex of this ligand to the asymmetric Diels-Alder reaction. Davies varied the link between the two oxazolines and found that cyclopropyl is the best connector (see catalyst 26), giving the cycloadduct of acryloyloxazolidinone and cyclopentadiene in high optical purity (98.4% ee) [35] (Scheme 1.45). Ghosh et al., on the other hand, obtained the same cycloadduct in 99% ee by the use of unsubstituted ligand (see catalyst 27) [36] (Scheme 1.46, Table 1.19). 

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. 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

On the other hand, several examples of chiral sulfonamides derived from ehiral a-amino acids have been successfully employed as ligands for enantio-seleetive Diels-Alder reactions. Thus, Yamamoto and Takasu have easily prepared new chiral Lewis acids from borane and sulfonamides of various ehiral a-amino acids, which were further studied for their abilities to promote the enantioselective Diels-Alder reaction between methacrolein and 2,3-dime-thyl-1,3-butadiene. Since 2,4,6-triisopropylbenzenesulfonamide of a-amino-butyric acid gave the highest enantioseleetivity, this eatalyst was applied to the... 

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... 

Recently, catalytic asymmetric Diels-Alder reactions have been investigated. Yamamoto reported a Bronsted-acid-assistcd chiral (BLA) Lewis acid, prepared from (R)-3-(2-hydroxy-3-phcnylphenyl)-2,2 -dihydroxy-1,1 -binaphthyl and 3,5A(trifluoromethy I) - be nzeneboronic acid, that is effective in catalyzing the enantioselective Diels-Alder reaction between a,(3-enals and various dienes.62 The interesting aspect is the role of water, THF, and MS 4A in the preparation of the catalyst (Eq. 12.19). To prevent the trimerization of the boronic acid during the preparation of the catalyst, the chiral triol and the boronic acid were mixed under aqueous conditions and then dried. Using the catalyst prepared in this manner, a 99% ee was obtained in the Diels-Alder reaction... 

For the preparation of enantiopure products, chiral aldehydes, chiral 1,3-dicar-bonyl compounds as well as chiral Lewis acids [375, 376] can be used. 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Given the prevalence of bis(oxazoline)-copper catalysts as chiral Lewis acids, it seems appropriate to comment briefly on catalyst preparations, since differences arise in the nature of the catalyst complex. Triflate-derived catalysts are formed simply by combining the ligand and Cu(OTf)2 in a given solvent and stirring for an appropriate length of time (typically >2 h) to achieve complete dissolution and complexation, Scheme 14. The hydrated version is formed by addition of 2 equiv of water to this catalyst solution, followed by removal of solvent after 15 min of stirring. The hydrated triflate catalyst is bench stable for months. 

As the chiral Lewis acids, cyclic dialkoxydichlorotitaniums(IV) were chosen and prepared in situ from various chiral 1,2- or 1,4-diols and... 

Starting from Fluoral Fluoral (trifluoroacetaldehyde) is an unstable gas that must be prepared before use by dehydration of the corresponding hydrate (commercially available). In spite of this limitation, fluoral itself has been used as a substrate in various reactions. Among the most recent examples, carbonyl-ene and hetero-Diels-Alder reactions deserve mention. The use of chiral Lewis acid... 

The initial work on the asymmetric [4-1-2] cycloaddition reactions of A -sulfinyl compounds and dienes was performed with chiral titanium catalysts, but low ee s were observed <2002TA2407, 2001TA2937, 2000TL3743>. A great improvement in the enantioselectivity for the reaction of AT-sulfinyl dienophiles 249 or 250 and acyclic diene 251 or 1,3-cyclohexadiene 252 was observed in the processes involving catalysis with Cu(ll) and Zn(ii) complexes of Evans bis(oxazolidinone) (BOX) ligands 253 and 254 <2004JOC7198> (Scheme 34). While the preparation of enantio-merically enriched hetero-Diels-Alder adduct 255 requires a stoichometric amount of chiral Lewis acid complex, a catalytic asymmetric synthesis of 44 is achieved upon the addition of TMSOTf. 

Similar facial selectivity has been observed in nitronates derived from chiral vinyl ethers (69), as well as from nitronates prepared with a chiral Lewis acid, which lack any bias from a chiral auxiliary (66). Even in the absence of a substituent at C(4), as in the nitronate 287, there remains a high facial selectivity upon the addition of a dipolarophile (Eq. 2.28) (84). Both RHE and B3LYP calculations for the approach of a dipolarophile to the nitronates 289 and 290 show at least a... 

Asymmetric Mannich reactions provide useful routes for the synthesis of optically active p-amino ketones or esters, which are versatile chiral building blocks for the preparation of many nitrogen-containing biologically important compounds [1-6]. While several diastereoselective Mannich reactions with chiral auxiliaries have been reported, very little is known about enantioselective versions. In 1991, Corey et al. reported the first example of the enantioselective synthesis of p-amino acid esters using chiral boron enolates [7]. Yamamoto et al. disclosed enantioselective reactions of imines with ketene silyl acetals using a Bronsted acid-assisted chiral Lewis acid [8]. In all cases, however, stoichiometric amounts of chiral sources were needed. Asymmetric Mannich reactions using small amounts of chiral sources were not reported before 1997. This chapter presents an overview of catalytic asymmetric Mannich reactions. 

Although asymmetric reactions using chiral Lewis acids are of great current interest as one of the most efficient methods for the preparation of chiral compounds, examples using imines as electrophiles are rare compared to those us-... 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

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