Asymmetric alkali-metal catalyst

Asymmetric Diels-Alder reaction mediated by alkali metal Lewis acid has been developed with optically active diene or dienophile [26-28]. On the other hand, asymmetric Diels-Alder reaction using chiral alkali metal catalyst is few. Probably, since alkali metal Lewis acid is generally a mild Lewis acid, chiral alkali metal... 

Scheme 5-45 Asymmetric hydrophosphonyla- nomenclature first letter = rare earth (L=La) tion ofimines catalyzed by heterobimetallic rare second letter = alkali (L = lithium, S = sodium, earth/alkali metal/BINOLcomplexes. Catalyst P = potassium)...

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... 

Significant improvement in the catalytic activity of ALB was realized without any loss of enantioselectivity by using the second-generation ALB [27] generated by the self-assembled complex formation of ALB with alkali metal-malonate or alkoxide. This protocol allowed the catalyst loading to be reduced to 0.3 mol %, for example, the Michael addition of methyl malonate to cyclohexenone catalyzed by the self-assembled complex of (ff)-ALB (0.3 mol %) and KO Bu (0.27 mol %) in the presence of MS 4A gave the adduct in 94% yield and 99% ee [28]. This reaction has been successfully carried out on a 100-g scale wherein the product was purified by recrystallization. The kinetic studies of the reactions catalyzed by ALB and ALB/Na-malonate have revealed that the reactions are second-order to these catalysts (the rate constant ALB = 0.273 M 1h 1 ALB/Na-maionate = 1-66 M 1h 1) [27]. This reaction was used as the first key step for the catalytic asymmetric total synthesis of tubifolidine (Scheme 8D. 11) [28]. 

In contrast, asymmetric Michael reactions are promoted by alkali metal free La-BINOL ester enolate complexes (Scheme 28) [251]. The catalyst is best prepared by successive addition of the Michael donor and (S)-BINOL to La(0 Pr)3. 

It was proposed that a Lewis acid lanthanum center controls the direction of the carbonyl function and activates the enone while the sodium alkoxide forms enolate intermediates and regenerates the catalyst by hydrogen abstraction (Scheme 6). Other Ln/alkali metal combinations, including La/Li, show negligible asymmetric induction, yet give almost racemic products in excellent yield. In contrast, alkali-metal free BINOL ester enolate complexes catalyze Michael reactions with high enantioselectivities, albeit at lower temperatures. 

The catalytic asymmetric epoxidation of a,/5-unsaturated ketones with hydroperoxides such as tert-butyl hydroperoxide (TBHP) and cumene hydroperoxide (CMHP) can be carried out at ambient temperature by using alkali-metal free Ln-BINOL complexes (eq. (22)) [184]. The oligomeric structure of the catalyst is assumed to play a key role that is, the Ln alkoxide moiety acts as a Brpnsted base, activating a hydroperoxide molecule, while another Ln metal ion acts as a Lewis acid, both activating and controlling the orientation of the enone. 

While hydroamination catalysts based on transition metals have been studied intensively over the past two decades, only a limited number of reports on alkali metal based hydroamination catalysts have emerged, although the first reports date back 60 years [71]. In particular, the application of chiral alkali metal complexes in asymmetric hydroamination of nonactivated aminoalkenes has drawn little attention to date [72, 73]. Also, attempts to perform asymmetric hydroamination utilizing... 

In order to broaden the scope of the amine-catalyzed Michael addition, Yamaguchi examined the system of amine and alkali metal salt [2]. Although amine did not promote the addition of malonate to enones, the LiCl04-Et3N catalyst turned out to be effective. Optically active amines, however, gave racemic adducts. As an extension, the (S)-proline rubidium salt, (S)-21, was developed, which possessed a cation and an amine moiety in the same molecule [2, 22]. The catalyst (S)-21 in chloroform promoted the asymmetric addition of malonate to a wide range of enones and enals as exemplified by the reaction of... 

The use of alkali metal-containing, heterobimetallic lanthanoid complexes as catalysts in asymmetric synthesis is reviewed. This new and innovative type of chiral catalyst, which was recently developed by Shibasaki et al., contains a Lewis acid as well as a Bronsted base moiety, thereupon showing a similar mechanistic effect as observed in enzyme chemistry. The heterobimetallic complexes have been successfully applied as highly stereoinducing catalysts in many different types of asymmetric reactions, including the stereoselective formation of C-C, C-O, and C-P bonds. 

In the presence of the sodium-containing heterobimetallic catalyst (R)-LSB (10 mol%), the reaction of enone 52 with TBHP (2 equiv) was found to give the desired epoxide with 83% ee and in 92% yield [56]. Unfortunately LSB as well as other bimetallic catalysts were not useful for many other enones. Interestingly, in marked contrast to LSB an alkali metal free lanthanoid BINOL complex, which was prepared from Ln(0- -Pr)3 and (R)-BINOL or a derivative thereof (1 or 1.25 molar equiv) in the presence of MS 4A (Scheme 17), was found to be applicable to a range of enone substrates. Regarding enones with an aryl-substitu-ent in the a-keto position, the most effective catalytic system was revealed when using a lanthanum-(.R/)-3-hydroxymethyl-BINOL complex La-51 (l-5mol%) and cumene hydroperoxide (CMHP) as oxidant. The asymmetric epoxidation proceeded with excellent enantioselectivities (ees between 85 and 94%) and yields up to 95%. 

Systems that combine a crown ether-like structure with an appropriately positioned k system have proven to form effective binding sites for alkali metal cations. Cation-n interactions were also used to incorporate n facial selectivity into catalysts for asymmetric synthesis. ... 

In this chapter, we reviewed recent developments regarding lithium, sodium, and potassium salt based-catalysis, with a particular focus on asymmetric catalysts. While these alkali-metal salts have traditionally been used as simple bases, recent advances based on chiral multifunctional acid-base combination chemistry, using chiral crown-alkali-metal complexes, chiral lanthanoid/alkali-metal complexes, chiral alkali-metal alkoxides, and chiral alkali-metal phosphates, have also been outstanding. These synergic acid-base catalyst systems should enable more efficient and/or new transformations that have not been possible thus far using conventional catalysts that only rely on Lewis acidity or Bronsted/Lewis basicity. 

One of the more reactive and selective catalysts of this type involves a bifunctional catalyst containing an alkali metal cation and an anionic lanthanide complex resulting from addition of excess binolate with lanthanide halides. Such catalysts have been used in asymmetric nitroaidol (Henry) reactions of ketones. Heterobimetallic Li-La alkoxo complexes (Figure 4.15) catalyzed these reactions with particularly high enantioselectivity. ... 

Hydrophosphonylation, Nitroaldol Reaction (Kaneka Co., Hokko Chemical Industry). First industrial applications of the heterobimetallic catalysts developed by Shibasaki were realized for the synthesis of several chiral-building blocks. The catalysts are aluminum or lanthanoid cations coordinated to two and three binol ligands, respectively. In addition, one or several alkali metals are coordinated to the binol as well. The asymmetric hydrophosphonylation methodology (85) is now being applied to the preparation of several a-amino phosphonic acids... 

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