Lewis aluminum, chiral

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]. 

As a recent progress on chiral aluminum Lewis acids, chiral Al(salen) complexes (25) developed by Jacobsen s group were found to be one of the most useful asymmetric catalysts for enantioselective 1,4-addition to a,P-unsaturated carbonyls (Figure 6.4) [110]. Jha and Joshi also reported the Al-Na bimetallic catalyst prepared from SALEN and Red-Al for Michael addition of malonic diesters to cyclic enones. [Ill]... 

Stereoselective All lations. Ben2ene is stereoselectively alkylated with chiral 4-valerolactone in the presence of aluminum chloride with 50% net inversion of configuration (32). The stereoselectivity is explained by the coordination of the Lewis acid with the carbonyl oxygen of the lactone, resulting in the typ displacement at the C—O bond. Partial racemi2ation of the substrate (incomplete inversion of configuration) results by internal... 

Chiral aluminum catalyst 2, prepared from Et2AlCl and a Vaulted biaryl ligand, is reported to be an effective Lewis acid catalyst of the Diels-AIder reaction between methacrolein and cyclopentadiene, affording the adduct in 97.7% ee [4] (Scheme 1.2). Although the Diels-AIder reaction with other a,/ -unsaturated aldehydes has not been described, that only 0.5 mol% loading is sufficient to promote the reaction is a great advantage of this catalyst. 

The most commonly used traditional Lewis acids are halides of aluminum, boron, titanium, zinc, tin, and copper. However, there are also more complex Lewis-acids that are quite effective catalysts that can be easily modified for carring out enantioselective processes, by incorporating chiral ligands. These can overcome some limitations associated with the use of classical Lewis acids [47]. 

In spite of the modest asymmetric induction it was concluded that at least one of the chiral ligands is coordinated to the nickel in the catalyticaUy active species. An alternative interpretation was given by Wilke and coworkers [29]. They could show that (methylsalicyhdene)dimethylaluminum forms a stable adduct with nickel(O) complexes. It was concluded that the asymmetric induction in Pino s experiment might be attributed to a complex in which the chiral Hgand is complexed to the Lewis acidic aluminum. 

This finding is also in agreement with another three-component Michael/aldol addition reaction reported by Shibasaki and coworkers [14]. Here, as a catalyst the chiral AlLibis[(S)-binaphthoxide] complex (ALB) (2-37) was used. Such hetero-bimetallic compounds show both Bronsted basicity and Lewis acidity, and can catalyze aldol [15] and Michael/aldol [14, 16] processes. Reaction of cyclopentenone 2-29b, aldehyde 2-35, and dibenzyl methylmalonate (2-36) at r.t. in the presence of 5 mol% of 2-37 led to 3-hydroxy ketones 2-38 as a mixture of diastereomers in 84% yield. Transformation of 2-38 by a mesylation/elimination sequence afforded 2-39 with 92 % ee recrystallization gave enantiopure 2-39, which was used in the synthesis of ll-deoxy-PGFla (2-40) (Scheme 2.8). The transition states 2-41 and 2-42 illustrate the stereochemical result (Scheme 2.9). The coordination of the enone to the aluminum not only results in its activation, but also fixes its position for the Michael addition, as demonstrated in TS-2-41. It is of importance that the following aldol reaction of 2-42 is faster than a protonation of the enolate moiety. 

Numerous asymmetric reactions using chiral aluminum Lewis acids have been developed some examples are shown in Scheme 73.313-315... 

This procedure describes the preparation and application of an effective chiral catalyst for the enantioselective Diels-Alder reaction.11 The catalyst is derived from optically active 1,2-diphenylethylenediamine, the preparation of which (either antipode) was described in the preceding procedure. The aluminum-based Lewis acid also catalyzes the cycloaddition of crotonoyl oxazolidinones with cyclopentadiene,11 and acryloyl derivatives with benzyloxymethylene-cyclopentadiene. The latter reaction leads to optically pure intermediates for synthesis of prostaglandins.11... 

Perhaps the most attractive method of introducing enantioselectivity into the Diels-Alder reaction is to use a chiral catalyst in the form of a Lewis acidic metal complex. In recent years, this area has shown the greatest progress, with the introduction of many excellent catalytic processes. Quite a number of ligand-metal combinations have been evaluated for their potential as chiral catalysts in Diels-Alder reactions. The most commonly used metals are boron, titanium, and aluminum. Copper, magnesium, and lanthanides have also been used in asymmetric catalytic Diels-Alder reactions. 

Enantioselective cydizations by radical additions to olefins have been reported and a few of them have already been discussed in Sect. 2.2.1. Cycliza-tions were performed by Nishida et al. using chiral aluminum Lewis acid... 

Oppolzer and colleagues performed pioneering work on the application of chiral sultam based dienophiles in asymmetric Diels-Alder reactions. The bomanesultam based dienophiles provided excellent de values in the Lewis acid mediated Diels-Alder reactions with a wide variety of dienes179. The efficiency of the simpler toluene-2,a-sultam based dienophiles was also studied180. Chiral auxiliary 282 proved superior to 283 and 284 in the aluminum Lewis acid catalyzed Diels-Alder reactions of its A-acryloyl derivative with cyclopentadiene, 1,3-butadiene and isoprene, affording the adducts with >90% de. 

Shibasaki et al. developed a polymer-supported bifunctional catalyst (33) in which aluminum was complexed to a chiral binaphtyl derivative containing also two Lewis basic phosphine oxide-functionahties. The binaphtyl unit was attached via a non-coordinating alkenyl Hnker to the Janda Jel-polymer, a polystyrene resin containing flexible tetrahydrofuran-derived cross-Hnkers and showing better swelling properties than Merifield resins (Scheme 4.19) [105]. Catalyst (33) was employed in the enantioselective Strecker-type synthesis of imines with TMSCN. 

The chiral dialuminum Lewis acid 14, which is effective as an asymmetric Diels-Alder catalyst, has been prepared from DIBAH and BINOL derivatives (Scheme 12.12). " The catalytic activity of 14 is significantly greater than that of monoaluminum reagents. The catalyst achieves high reactivity and selectivity by an intramolecular interaction of two aluminum Lewis acids. Similarly, the chiral trialuminum Lewis acid 15 is quantitatively formed from optically pure 3-(2,4,6-triisopropylphenyl)binaphthol (2 equiv) and MeaAl (3 equiv) in CH2CI2 at room temperature (Scheme 12.12). " The novel structure of 15 has been ascertained by NMR spectroscopic analysis and measurement of the methane gas evolved. Trinuclear aluminum catalyst 15 is effective for the Diels-Alder reaction of methacrolein with cyclopentadiene. Diels-Alder adducts have been obtained in 99% yield with 92% exo selectivity. Under optimum reaction conditions, the... 

The real promise of this catalytic reaction is the eventual development of an efficient enantioselective allylboration catalyzed by chiral Lewis acids. A stereoselective reaction using a substoichiometric amount of a chiral director has been reported, but only modest levels of stereo-induction were achieved with an aluminum-BINOL catalyst system (Eq. 19)P Recently, a chiral Brpnsted acid catalyzed system has been devised based on a diol-tin(IV) complex (Eq. 80). In this approach, aliphatic aldehydes provide enantioselectivities (up to 80% ee) higher than those of aromatic aldehydes when using the optimal complex 114. Although the levels of absolute stereoselectivity of this method remain too low for practical uses, promising applications are possible in double diastereoselection (see section on Double Diastereoselection ). 

Lewis acids have also been found to promote the electrophilic cleavage of cyclobutanes. The key feature of this reaction can be depicted by the conversion of the chiral 4-(2-hydroxy-6-methoxyphenyl)-6,6-dimethylbicyclo[3.1.1]heptan-2-ones 5 and 4-(2-methoxy-6-hydroxyphenyl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-ones 7 to (6a5, 10a/ )-(-)-l-methoxy-6,6a,7,8,10,10a-hexahydro-6,6-dimethyl-9//-dibenzo[b,c/]pyran-9-ones 6 and (6aS)-( + )-methoxy-6,6a,7,8-tetrahydro-6,6-dimethyl-9//-dibcnzo[b//]pyran-9-ones 8, respectively, on treatment with either tin(IV) chloride in chloroform or with aluminum trichloride in dichloromethane.52... 

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... 

Yamamoto et al. have reported the asymmetric catalysis of a chiral Lewis acid in a carbonyl-ene reaction, which uses chloral as the enophile and an aluminum catalyst with enantiopure 3,3 -bissilylated binaphthol (BINOL) to give the corresponding homoallylic alcohol with 78% ee in 79% yield (Scheme 8C.2) [6]. It should be noted that 3,3 -diphenyl-BINOL-derived aluminum catalyst provides the racemic product in low yield. 

This idea was realized very successfully by Shibasaki and Sasai in their heterobimetallic chiral catalysts [17], Two representative well-defined catalysts. LSB 9 (Lanthanum/Sodium/BINOL complex) and ALB 10 (Aluminum/Lithium/BINOL complex), are shown in Figure 8D.2, whose structures were confirmed by X-ray crystallography. In these catalysts, the alkali metal (Na, Li, or K)-naphthoxide works as a Br0nsted base and lanthanum or aluminum works as a Lewis acid. 

In one of the earliest reports on enantioselective radical reactions, chiral Lewis acid mediated conjugate addition followed by enantioselective H-atom transfer a to a carbonyl was reported by Sato and co-workers (Scheme 3) [22], The single point binding chiral aluminum complex presumably coordinates to the carbonyl oxygen of the lactone as shown in 10. The strong Lewis acidity of the aluminum complex activates the substrate 7 to nucleophilic conjugate addition, which is followed by an enantioselective H-atom transfer from BuaSnH in a chiral environment provided by BINOL ligand in 8. Only 28% ee was observed for product 9. 

These chiral C2 symmetric 1,2-diamines have been used to prepare chiral reagents containing aluminum or boron, which have proved to be highly effective Lewis acid catalysts for several synthetic reactions. 

However, it could be shown that in principle simple imines can be used successfully as well for asymmetric aminoalkylation reactions catalyzed by chiral Lewis acids. The asymmetric allylation of simple imines 16 with allyltributylstannane (Scheme 6) catalyzed by the / -pinene derivative 17 [32a], for example furnished comparatively good results (for related asymmetric catalytic allylations of simple imines, see [32b-d]). Moreover, it was demonstrated on the basis of several Strecker-type syntheses [33-35] that catalysts such as the chiral aluminum complex 18 (Scheme 6) [33a—b] are also well suited for enantioselective aminoalkylations with simple imines. The mechanism indicated in Scheme 6 shows that the... 

Next, the mechanism of the Type II reactions is discussed. To discriminate one of the enantiofaces of the acceptor it is desirable to place and to activate the electrophiles in a chiral environment. At the same time, effective activation of the Michael donor is required. In Shibasaki s ALB-catalyzed reaction (Scheme 3), it was proposed that the aluminum cation functioned as a Lewis acid to activate enones at the center of the catalyst, and that the Li-naphthoxide moiety deproton-ated the a-hydrogen of malonate to form the Li enolate (Scheme 9). Such simultaneous activation of both reactants at precisely defined positions became feasible by using multifunctional heterobimetallic complexes the mechanism is reminiscent of that which is operative in the active sites of enzymes. The observed absolute stereochemistry can be understood in terms of the proposed transition state model 19. Importantly, addition of a catalytic amount of KOt-Bu (0.9equiv. to ALB) was effective in acceleration of the reaction rate with no deterioration of the... 

Scheme 3. Catalytic asymmetric aldol reaction with aluminum- and tin-containing chiral Lewis acids a) Reetz and b) Mukaiyama.

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