Heterobimetallic asymmetric catalysis

Our preliminary attempts to obtain a basic chiral rare earth complex led us to create several new chiral heterobimetallic complexes which catalyze different types of asymmetric reaction. The rare earth-alkali metal-tris(l,l -bi-2-naphthoxide) complexes (LnMB, where Ln = rare earth, M = alkali metal, and B = l,l -bi-2-naphthoxide) have been efficiently synthesized from the corresponding metal chloride or alkox-ide [46 9], and the structures of the LnMB complexes have been unequivocally determined by a combination of X-ray crystallography and LDI-TOF-mass spectroscopy, as shown in Fig. 3 [50-53]. 

For example, an effective procedure for the synthesis of LLB (where LL = lanthanum and lithium) is treatment of LaCls 7H2O with 2.7 mol equiv. BINOL dilithium salt, and NaO-t-Bu (0.3 mol equiv.) in THF at 50 °C for 50 h. Another efficient procedure for the preparation of LLB starts from La(0-/-Pr)3 [54], the exposure of which to 3 mol equiv. BINOL in THF is followed by addition of butyllithium (3 mol equiv.) at 0 C. It is worthy of note that heterobimetallic asymmetric complexes which include LLB are stable in organic solvents such as THF, CH2CI2 and toluene which contain small amounts of water, and are also insensitive to oxygen. These heterobimetallic complexes can, by choice of suitable rare earth and alkali metals, be used to promote a variety of efficient asymmetric reactions, for example nitroaldol, aldol, Michael, nitro-Mannich-type, hydrophosphonylation, hydrophosphination, protonation and Diels-Alder reactions. A catalytic asymmetric nitroaldol reaction, a direct catalytic asymmetric aldol reaction, and a catalytic asymmetric nitro-Mannich-type reaction are discussed in detail below. 

The nitroaldol (Henry) reaction has been recognized as a powerful synthetic tool and has been used in the construction of numerous natural products and other useful compounds. We succeeded in realizing the first example of a catalytic asymmetric nitroaldol reaction by the use of a catalytic amount of LLB. 

Having succeeded in obtaining the first results from a catalytic asymmetric nitroaldol reaction, we attempted to apply the method to the catalytic asymmetric synthesis of biologically important compounds. The nitroaldol products were readily converted into /3-amino alcohols and/or ct-hydroxy carbonyl compounds and convenient syntheses of three kinds of optically active /1-blocker are presented in Sch. 8 [55-57]. 

With more effective asymmetric catalysts in hand, we next applied the most efficient catalysts 27 and 28 to diastereoselective nitroaldol reactions. We were very pleased to find that high syn selectivity and enantioselectivity were always obtained by use of 3.3 mol % catalyst [58]. Representative results are listed in Table 14. 

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M Shibasaki, H. Sasai, T. Arai, Asymmetric Catalysis with Heterobimetallic Compounds, Angew. Chem Int. Ed Engl 1997, 36,1236-1256. 

Asymmetric catalysis of the Pudovik reaction is an area of active study with numerous success stories, mostly featuring chiral Lewis acid catalysts, and further developments are anticipated.39,86,87 Shibasaki and co-workers heterobimetallic catalysts108 are the best developed in this field, for both aldehyde and aldimine substrates. 

During the last decade Shibasaki and co-workers focussed on the application of rare earth metal catalysts with special properties [2]. More recently, impressive studies by this group revealed the broad applicability of chiral heterobimetallic catalysts based on rare earth metal alkoxide complexes in asymmetric catalysis. Whereas initial... 

Shibasaki, M. Sasai, H. Asymmetric Catalysis Using Heterobimetallic Compounds, Adv. Asym. Synth., Vol. 3, Hassner, A., Ed., JAI Press, Stamford, CT, 1998. 

Lanthanides Containing Multifunctional Heterobimetallic and Heteropolymetallic Asymmetric Catalysis... 

Scheme 1. Catalytic asymmetric nitroaldol reaction promoted by heterobimetallic lanthanoid catalysis LnLB...

In 1992, Shibasaki et al. reported for the time an application of chiral heterobimetallic lanthanoid complexes (LnLB) as chiral catalysts in asymmetric catalysis, namely the catalytic asymmetric nitroaldol reaction (Henry reaction), which is one of the most classical C-C bond forming processes [11]. Additionally, this work represents the first enantioselective synthesis of (3-nitroalcohol compounds by the way of enantioselective addition of nitroalkanes to aldehydes in the presence of a chiral catalyst. The chiral BINOL based catalyst was prepared starting from anhydrous LaCl3 and an equimolar amount of the dialkali metal salt of BINOL in the presence of a small amount of water [9]. 

Books 1. Ojima, Catalytic Asymmetric Synthesis , VCH, New York, 1993 R. Noyori, Asymmetric Catalysis in Organic Synthesis , John WUey Sons, New York, 1994 T. Hayashi, K. Tomioka, O. Yonemitsu, Asymmetric Synthesis , Kodansha/Gordon and Breach Science Publishers, Tokyo, 1998 J. Seyden-Penne, Chiral AuxUiaries and Ligands in Asymmetric Synthesis , John Wiley Sons, New York, 1995 Recent Reviews M. Shibasaki, H. Sasai, T. Aral, Angew. Chem. 1997, 109, 1290 Angew. Chem., Int. Ed. 1997, 36, 1237 (Asymmetric Catalysis with Heterobimetallic Compounds), S. Koba-yashi, PureAppl Chem. 1998, 70, 1019 (New Types of Lewis Acids Used in Organic Synthesis), K. Mikami, Pure Appl. Chem. 1996, 68, 639 (Asymmetric Catalysis of Carbo-nyl-Ene Reactions and Related Carbon-Carbon Bond Forming Reactions). 

The first example of application of a chiral early-late heterobimetallic complex in asymmetric catalysis was reported by Bomer in 1999 and deals with hydroformylation of activated olefins (Scheme 39) [122]. The chiral bimetallic complex 66 was generated in situ by reacting the (R,R)-Diph-salenophos-Ti(0 Pr)2 ligand (67) with [Rh(acac)(CO)2]. This complex gives rise to a diminished conversion in aldehyde (21 % vs 99%) as well as a lower selectivity (i n = 77/23 vs 99/1) with respect to the monometallic salenophos-Rh complex generated in situ from the free-metal ligand 68 and [Rh(acac)(CO)2] but affords the branched aldehyde with 30% ee. 

Shibasaki M, Sasai H, Arai T. Asymmetric catalysis with heterobimetallic compounds. Angew. Chem. Int. Ed. 1997 36 1236-1256. 

The first catalytic asymmetric aza-Henry reaction appears to have been reported by Shibasaki in 1999, as part of a general research program focused on heterobimetallic lanthanide complexes and their application in asymmetric catalysis [190]. In the event, a 1 1 3 mixture of KOt-Bu, Yb(Oi-Pr)3, and (i )-BINOL afforded an active catalyst suggested to have the structure 302 (Equation 32) [191]. This catalyst was shown to promote enantioselective additions of nitromethane to N-phosphinoylarylimines, including 300, to provide the corresponding products, such as 303, in 79 % yield and 91 % ee. 

Conceptually new multifunctional asymmetric two-center catalysts, such as the Ln-BINOL derivative, LnMB, AMB, and GaMB have been developed. These catalysts function both as Brpnsted bases and as Lewis acids, making possible various catalytic, asymmetric reactions in a manner analogous to enzyme catalysis. Several such catalytic asymmetric reactions are now being investigated for potential industrial applications. Recently, the catalytic enantioselective opening of meso epoxides with thiols in the presence of a heterobimetallic complex has... 

Heterobimetallic catalysis mediated by LnMB complexes (Structures 2 and 22) represents the first highly efficient asymmetric catalytic approach to both a-hydro and c-amino phosphonates [112], The highly enantioselective hydrophosphonylation of aldehydes [170] and acyclic and cyclic imines [171] has been achieved. The proposed catalytic cycle for the hydrophosphonylation of acyclic imines is shown representatively in Scheme 10. Potassium dimethyl phosphite is initially generated by the deprotonation of dimethyl phosphite with LnPB and immediately coordinates to the rare earth metal center via the oxygen. This adduct then produces with the incoming imine an optically active potassium salt of the a-amino phosphonate, which leads via proton-exchange reaction to an a-amino phosphonate and LnPB. 

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

The application of the heterobimetallic lanthanoid complexes of the LnMB type led to a breakthrough in establishing a highly efficient asymmetric catalytic route to a-hydroxy as well as a-amino phosphonic acid esters, which have attracted much attention due to their wide ranging biological activity [57-64]. The heterobimetallic catalysis described below represents the first and until now the only highly efficient asymmetric catalytic approach to both a-hydroxy and a-amino phosphonates by the attractive way of asymmetric catalytic hydrophos-phonylation. 

Since these initial publications, the considerable efforts of Shibasaki and coworkers have lead to lanthanide element-binaphtholato complexes as being the most developed and potent of asymmetric phospho-aldol catalysts. From their early work on catalysis in the nitro-aldol reaction [28], Shibasaki and co-workers have published widely and in considerable detail on the use of hetero-bimetallic catalysis, developing the field to such a degree that enzyme-like comparisons have been made. Much of the success of the Shibasaki team in hetero-bimetallic catalysis has been reviewed recently [29], the key to which has been the delineation of the solid state structures of the catalytic precursors via single crystal X-ray diffraction studies [30] (Fig. 1) and the development of improved synthetic routes to this class of heterobimetallic system (Scheme 12) which emphasise the important role of added water [31]. 

A heterobimetallic Ga/cationic Yb/Schiff base complex as a Lewis acid/Lewis acid bifimctional catalyst catalyzes asymmetric a-addition of a-isocyanoacetamides to aryl, heteroaryl, alkenyl, and alkyl aldehydes (Scheme 6). The Schiff base derived from o-vanillin was suitable to utilize cationic rare earth metal triflates with good Lewis acidity in bimetallic Schiff base catalysis. 

Although heterobimetallic complexes afforded nitroaldol adducts in good stereoselectivity, most reactions required a long reaction time even with relatively high catalyst loadings (3-10 mol%). To achieve a more efficient catalysis, a strategy to accelerate the reaction was investigated. A plausible mechanism of catalytic asymmetric nitroaldol reaction is shown in Scheme 13.42. The concentration of intermediate (A) was considered to be rather low in the reaction mixture because of an... 

Heterobimetallic Catalysis with Amide-Based Ligand 3.1 Anti-Selective Catalytic Asymmetric Nitroaldol Reaction... 

In this chapter, recent achievements in asymmetric cooperative catalysis exploiting the power of multimetallic catalysts are described. The three types of multidentate ligands, Schiff base ligands, amide-based ligands, and sugar-derived ligands, serve as a suitable platform for the construction of homobimetallic, heterobimetallic, and... 

Similar hypothesis of this kind of cooperative catalysis mechanism has been proposed by Matsunaga, Shibasaki, and co-workers in their heterobimetallic gal-lium/ytterbium-Schiff base complex catalyzed asymmetric oc-addition of isocyanides to aldehydes [99]. Research along this line will be reviewed in another chapter of this book [100]. 

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