Aluminum-lithium-BINOL complex

Shibasaki showed that an aluminum-lithium-BINOL complex (ALB) also catalyzes the asymmetric addition of dialkyl phosphites to aldehydes, with ees ranging from 55 to 90% for aryl or unsaturated aldehydes (Scheme 5-37). 

R)-aluminum-lithium-BINOL complex (0.024 g, 0.04 mmol) was dissolved in toluene (0.4 ml), and to this solution was added dimethyl phosphite (0.044 g, 0.4 mmol) at room temperature the mixture was stirred for 30 min. Benzaldehyde (0.042 g, 0.4 mmol) was then added at -40°C. After having been stirred for 51 h at -40°C, the reaction mixture was treated with 1 N hydrochloric acid (1.0 ml) and extracted with ethyl acetate (3 x 10 ml). The combined organic extracts were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by flash chromatography (silica, 20% acetone/hexane) to give the diethyl (S)-a-hydroxybenzylphosphonate (78 mg, 90%) with 85% enantiomeric excess as a colorless solid of mp 86 to 87°C. 

Moreover, these rare earth heterobimetallic complexes can be utilized for a variety of efficient catalytic asymmetric reactions as shown in Scheme 7 Next we began with the development of an amphoteric asymmetric catalyst assembled from aluminum and an alkali metal.1171 The new asymmetric catalyst could be prepared efficiently from LiAlH4 and 2 mol equiv of (R)-BINOL, and the structure was unequivocally determined by X-ray crystallographic analysis (Scheme 8). This aluminum-lithium-BINOL complex (ALB) was highly effective in the Michael reaction of cyclohexenone 75 with dibenzyl malonate 77, giving 82 with 99% ee and 88 % yield at room temperature. Although LLB and... 

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. 

Another highly useful heterobimetallic catalyst is the aluminum-lithium-BINOL complex (ALB) prepared from LiAlH4 and 2 equiv. of (/ )-BINOL. The ALB catalyst (10 mol %) is also effective in the Michael reaction of enones with various malonates, giving Michael products generally with excellent enantioselectivity (91-99% ee) and in excellent yields [23]. These results ate summarized in Table 8D.3. Although LLB and LSB complement each other in their ability to catalyze asymmetric nitroaldol and Michael reactions, respectively, the Al-M-(/ )-BINOL complexes (M = Li, Na, K, and Ba) are commonly useful for the catalytic asymmetric Michael reaction. 

Among metal-BINOL complex catalysts developed by Shibasaki et al., (I )-ALB is found to be the most effective catalyst for the asymmetric Michael addition of malonate to 2-cyclohexen-l-one. In 1998, Shibasaki et al. further fine-tuned the reaction 9onditions by adding the base (e.g., KO-r-Bu) and MS (4 A) to the system. These optimizations accelerate the catalytic asymmetric Michael addition without lowering the enantioselectivity. They suggested that the base was used to activate the Aluminum-Lithium-BINOL (ALB) complex. The 4-A molecular sieve (MS) was used to remove the trace amount of H2O that could otherwise gradually lead to ALB-KO-f-Bu catalyst decomposition. In the presence of ALB (0.3 mol%), KO-f-Bu (0.27 mol%), and 4-A MS, the Michael addition of dimethyl malonate to cyclohex-2-enone proceeded smoothly to give 94% product yield with 99% ee even at room temperature. Particularly noteworthy was that this reaction could be carried out on a 100-g scale without deleterious effect. Later, Xu and co-workers modified and streamlined the work-up procedures... 

The structure of catalyst 428 was proposed as a result of the several experiments shown in Sch. 60 and discussed below [89]. Firstly, it was observed that treatment of ALB catalyst 394 (Sch. 51) with methyllithium produced a solution from which the hexacoordinate aluminum species 434 (M = Li) could be crystallized in 43 % yield. The same compound could also be obtained from solutions prepared from 394 and nBuLi, and the sodium enolate of 425. Solid-state X-ray analysis of this compound revealed that it has the same structiu-e as the species 417 (Sch. 56) isolated by Feringa and coworkers during the preparation of ALB with excess BINOL (Sch. 55) [86]. The tris-BINOL(tris-lithium) alimunum complex 434 is not the active catalyst in the Michael addition of phosphonate 425 to cyclohexenone because the use of this material as catalyst gave the Michael adduct 426 in 28 % yield and 57 % ee which is dramatically lower than obtained by use of catalyst 428 (Sch. 59). In addition, the use of catalyst 434 (M = Li) gave the alkene product 429 in 13 % yield, a product that was not seen with catalyst 428. Additional evidence comes from the reaction between 425 and cyclopentenone with catalyst 434 (M = Li) which gives the adduct 427 in 78 % yield and 12 % ee. 

The successful achievement of the (/ )-LSB catalyst in asymmetric Michael addition suggested that the metal centers other than rare earths might lead to a novel heterobime-talhc asymmetric catalyst with unique properties. With this foundation, the same group further developed a new heterobimetallic chiral catalyst (/ )-ALB consisting of aluminum, lithium, and (/ )-BINOL in 1996 (Table 9.3). They reported that this type of catalyst could be more efficiently prepared from LiAlH with two equivalents of (/ )-BINOL. When this AlLibis(binaphthoxide) complex (/ )-ALB was employed as catalyst, up to 99% ee and 88% yield of products could be obtained in the reaction of dibenzyl malonate to 2-cyclohexen-l-one. Notably, both dimethyl and diethyl malonates furnished the 1,4-adducts with more than 90% of enantioselectivities. In particular, the catalytic asymmetric tandem Michael-aldol reactions were also achieved in the presence of (/ )-ALB. This protocol provides a usefid method for the catalytic asymmetric synthesis of complex molecules. 

Other Metal Complexes Apart from metal complexes derived from BINOL, other metal complexes, such as the lithium-aluminum amiuo diol complex, " aluminum and nickel salen complex, ruthenium diamine complex, and ruthenium phosphinite diamine complex were also found applicable for the asymmetric Michael addition of 1,3-dicarbonyl compound to cyclic enone. All these metal complexes afforded about 90% of asymmetric induction in the Michael reaction of 2-cyclohexen-l-one and malonate. 

The structurally well-defined aluminum-lithium complex 124 was readily prepared by mixing two equivalents of BINOL with LiAlH4 (Scheme 12.15) [117]. It catalyzes the addition of dimethyl malonate (123) to cyclohexenone (122) to furnish adduct 125 in 99% ee and 95% yield. The substituted cyclohexanone 125 sei-ved as a key intermediate en route to the Sttychnos alkaloid tubifolidine (126) [118]. 

Shibasaki made several improvements in the asymmetric Michael addition reaction using the previously developed BINOL-based (R)-ALB, (R)-6, and (R)-LPB, (R)-7 [1]. The former is prepared from (R)-BINOL, diisobutylaluminum hydride, and butyllithium, while the latter is from (R)-BINOL, La(Oz -Pr)3, and potassium f-butoxide. Only 0.1 mol % of (R)-6 and 0.09 mol % of potassium f-butoxide were needed to catalyze the addition of dimethyl malonate to 2-cy-clohexenone on a kilogram scale in >99% ee, when 4-A molecular sieves were added [15,16]. (R)-6 in the presence of sodium f-butoxide catalyzes the asymmetric 1,4-addition of the Horner-Wadsworth-Emmons reagent [17]. (R)-7 catalyzes the addition of nitromethane to chalcone [18]. Feringa prepared another aluminum complex from BINOL and lithium aluminum hydride and used this in the addition of nitroacetate to methyl vinyl ketone [19]. Later, Shibasaki developed a linked lanthanum reagent (R,R)-8 for the same asymmetric addition, in which two BINOLs were connected at the 3-positions with a 2-oxapropylene... 

A mechanism for this reaction has been proposed and is summarized in Sch. 10. The catalyst 64 is thought to be bifunctional with the aluminum center operating as a Lewis acid and the lithium naphthoxide operating as a Lowry-Brpnsted base. It was envisaged that the aldehyde coordinates with the aluminum to give the complex 69 and deprotonation of the dimethyl phosphite then gives the aggregate 70 in which the phosphite anion is positioned for P-alkylation of the aldehyde that will occur selectively from the si face when the catalyst is prepared from (f )-BINOL. 

The first chiral aluminum catalyst for effecting asymmetric Michael addition reactions was reported by Shibasaki and coworkers in 1986 [82], The catalyst was prepared by addition of two equivalents of (i )-BINOL to lithium aluminum hydride which gave the heterobimetallic complex 394. The structure of 394 was supported by X-ray structure analysis of its complex with cyclohexenone in which it was found that the carbonyl oxygen of the enone is coordinated to the lithium. This catalyst was found to result in excellent induction in the Michael addition of malonic esters to cyclic enones, as indicated in Sch. 51. It had previously been reported that a heterobimetallic catalyst prepared from (i )-BINOL and sodium and lanthanum was also effective in similar Michael additions [83-85]. Although the LaNaBINOL catalyst was faster, the LiAlBINOL catalyst 394 (ALB) led to higher asymmetric induction. 

Inspired by the bimetallic catalyst developed by Shibasaki and coworkers with 2 1 complexes of BINOL with aluminum, Manickam and Sundararajan prepared 2 1 complexes of the aminodiol 420 with aluminum [87,88]. Reaction of malonate esters with cyclopentenone or cyclohexenone results in asymmetric induction of at least 90 % ee with dibutyl malonate, as detailed in Sch. 57. A catalyst prepared by the reaction of 2 equiv. diol 419 with lithium aluminum hydride was found to result in asymmetric induction for the reaction of cyclohexenone with malonate 390d similar to that observed with the catalyst derived from 420 and from BINOL, although the rate was slightly slower. 

An aluminum-lithiiun catalyst, (R)-ALB, prepared from (R)-BINOL, and lithium aluminium hydride promoted the addition of malonate to 23 giving (R)-44 in 99% ee. X-ray analysis of the ALB catalyst showed an aluminum ate complex structure with li coordination to the oxygen atom. The asymmetric tandem Michael-aldol reaction of 46 was conducted with this catalyst giving a single isomer 47 containing three asymmetric centers. The aluminum enolate under-... 

Shibasald s concept of a cooperative effect exhibited by two different metals (usually an alkali with a group 3 metal or a lanthanide) in heterobimetallic BINOL-derived complexes was also fruitful in consecutive Michael-aldol additions. Thus, Al-Li-bis[binaphthoxide] complex R,R)-449, readily accessible from lithium aluminum hydride and 2 equiv. of (S)-BINOL, functions as a highly... 

The key role of aluminum as the enolate metal for enabhng an in situ aldol addition was studied. Based thereupon, the catalytic cycle shown in Scheme 5.116 was proposed. Lithium enolate 454 is generated from cyclopentenone, complex 449, and malonate 448a. In this enolate complex 454, an oxygen atom of the BINOL... 

As a further modification of ALB catalyst, Feringa and coworkers reported a catalytic system derived from LiAlH4 and 2.45 equivalent of BINOL in THF for Michael addition of a-nitropropionates (Scheme 6.88) [108]. Al-NMR study of this catalytic system revealed the presence of three aluminum species. One of these was assigned as the hexacoordinate-aluminum complex (108a) composed of three BINOL ligands, one aluminum, and three lithium. 

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