Heterobimetallic lanthanoid catalysts

The catalytic asymmetric nitroaldol reactions promoted by LLB or its derivatives require at least 3.3 mol% of asymmetric catalysts for efficient conversion. However, even in the case of 3.3 mol% of catalyst, reactions are rather slow. Attempts were made to reduce the required catalytic amount and accelerate the reactions, which led to a second-generation heterobimetallic lanthanoid catalyst (LLB-II), prepared from LLB, 1 mol equiv of H20, and 0.9 mol equiv of butyllith-ium. The use of only 1 mol% of LLB-II efficiently promoted catalytic asymmetric nitroaldol reactions and additionally LLB-II (3.3 mol%) accelerated these reactions [32]. A comparison of the efficiency of LLB (or LL(B-a)) and the second-generation catalysts LLB-II (or LL(B-a)-II) is given in Scheme 9. The structure of LLB-II has not yet been unequivocally determined. However, it appears that it is a complex of LLB and LiOH. 

Although the development of a range of catalytic asymmetric aldol-type reactions has proven to be a valuable contribution to asymmetric synthesis [35—37], in all of these reactions pre-conversion of the ketone moiety to a more reactive species such as an enol silyl ether, enol methyl ether, or ketene silyl acetal has been an unavoidable necessity. However, quite recently Shibasaki et al. reported that a direct catalytic asymmetric aldol reaction, which is known in enzyme chemistry, is also possible in the presence of heterobimetallic lanthanoid catalysts [38]. Using fR)-LLB (20 mol%), which shows both Lewis acidity and Bron-sted basicity similar to the corresponding aldolases, the desired optically active aldol adducts were obtained with up to 94% ee. A variety of aldehydes and unmodified ketones can be used as starting materials (Scheme 11). 

A further application of the heterobimetallic lanthanoid catalysts of the LLB type to the field of catalytic asymmetric Diels-Alder reactions [47,48] was also achieved by Shibasaki et al. [49]. In general, LLB type complexes are multifunctional asymmetric catalysts, showing both Bronsted basicity and Lewis acidity. Nevertheless, in this study the use of LLB type catalysts acting as asymmetric Lewis acids alone was examined and led to the development of an LLB (type) catalyzed asymmetric Diels-Alder reaction [49]. Representative results for the catalytic asymmetric Diels-Alder reactions using 48 and cyclopentadiene in toluene as a solvent are shown in Scheme 16. 

Shibasaki M, Grdger H (1999) Chiral Heterobimetallic Lanthanoid Complexes Highly Efficient Multifunctional Catalysts for the Asymmetric Formation of C-C, C-O and C-P Bonds. 2 199-232... 

Shibasaki, M. and Groger, H. (1999) Chiral heterobimetallic lanthanoid complexes highly efficient multifunctional catalysts for the asymmetric formation of CC CO and CP bonds. Topics in Organometallic Chemistry, 2 (Lanthanides) 199-232. 

In 1992, Shibasaki et al. [8] reported for the first time on the use of recently developed chiral heterobimetallic lanthanoid complexes (LnLB) as chiral catalysts in the catalytic asymmetric Henry reaction (Scheme 1). In the following sections, this efficient concept of an asymmetric nitroaldol reaction, its scope and limitations, and its applications to complex stereoselective synthetic topics are described. 

A further example of a diastereoselective nitroaldol reaction using heterobimetallic lanthanoid complexes as catalysts was recently reported by Okamoto et... 

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. 

Concerning the heterobimetallic potassium lanthanoid catalysts (Pj-LnPB, a very recent NMR spectroscopic as well as FAB and ESI mass spectrometric study of isolated (Rj-YbPB complexes provided a clear insight into the assembly of this heterobimetallic complex in solution. At first, the assumption that the proposed... 

A further example of a diastereoselective nitroaldol reaction using heterobimetallic lanthanoid complexes as catalysts was recently reported by Okamoto et al. [18] in connection with a novel approach to lc/.,24( R)-dihydroxyvitamin D3... 

Some of the metal-based catalysts used in the asymmetric hydrophosphonylation of aldehydes (see Section 6.4) can also be applied to the phosphonylation of imines. For instance, Shibasaki s heterobimetallic BINOL complexes work well for the catalytic asymmetric hydrophosphonylation of imines. In this case lanthanum-potassium-BINOL complexes (6.138) have been found to provide the highest enantioselectivities for the hydrophosphonylation of acyclic imines (6.139). The hydrophosphonylation of cyclic imines using heterobimetallic lanthanoid complexes has been reported. Ytterbium and samarium complexes in combination with cyclic phosphites have shown the best results in the cases investigated so far. For example, 3-thiazoline (6.140) is converted into the phosphonate (6.141) with 99% ee using ytterbium complex (6.142) and dimethyl phosphite (6.108). The aluminium(salalen) complex (6.110) developed by Katsuki and coworkers also functions as an effective catalyst for the hydrophosphonylation of both aromatic and aliphatic aldimines providing the resulting a-aminophosphonate with 81-91% ee. ... 

Shibasaki and coworkers have developed lanthanoid-lithium-BINOL complexes (LLB catalysts) as efficient catalysts for the asymmetric nitroaldol (Henry) reaction (59-46). The heterobimetallic asymmetric catalysts effectively mediate the reaction of a variety of aldehydes with nitroalkanes to afford the corresponding desired nitroaldols with high enantioselectivity (Scheme 4). We examined the capability of the LLB complexes as asymmetric catalysts for the nitroaldol reaction of 2,2-difluoroaldehydes with nitromethane (47). 

Asymmetric catalytic addition of dialkylphosphites to a C=0 double bond is a powerful method, and probably the most general and widely applied, for formation of optically active a-hydroxy phosphonates [258], The basic principle of this reaction is shown in Scheme 6.108. Several types of catalyst have been found to be useful. The transition-metal-catalyzed asymmetric hydrophosphonylation using chiral titanium or lanthanoid complexes was developed by several groups [259, 260], The most efficient type of chiral catalyst so far is a heterobimetallic complex consisting... 

Keywords Heterobimetallic catalysts, Lanthanoid complexes, Asymmetric synthesis, Homogenous catalysis... 

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%. 

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... 

Lanthanoid triisopropoxides are active catalysts for aldol reactions of aldehydes (209). In addition, it is useful reagent for the preparation of Ln-based heter-obimetallic catalysts, such as LLB 160. Shibasaki and co-workers contributed an important progress in the Ln-based heterobimetallic catalysts promoted organic transformations, including the aldol reactions (210-212). For example, early in 1997, they reported the (i )-LLB catalyzed direct aldol reaction with good enantioselectivities (up to 94% ee) and yields (up to 90%) for the direct aldol reaction of ketones to aldehydes (Scheme 55) (213). 

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