Heterobimetallic asymmetric catalysts

The heterobimetallic asymmetric catalyst, Sm-Li-(/ )-BINOL, catalyzes the nitro-aldol reaction of ot,ot-difluoroaldehydes with nitromethane in a good enantioselective manner, as shown in Eq. 3.78. In general, catalytic asymmetric syntheses of fluorine containing compounds have been rather difficult. The S configuration of the nitro-aldol adduct of Eq. 3.78 shows that the nitronate reacts preferentially on the Si face of aldehydes in the presence of (R)-LLB. In general, (R)-LLB causes attack on the Re face. Thus, enantiotopic face selection for a,a-difluoroaldehydes is opposite to that for nonfluorinated aldehydes. The stereoselectivity for a,a-difluoroaldehydes is identical to that of (3-alkoxyaldehydes, as shown in Scheme 3.19, suggesting that the fluorine atoms at the a-position have a great influence on enantioface selection. 

Keywords Heterobimetallic Asymmetric Catalyst m Rare Earth Meta ... 

T. Arai, H. Sasai, K. Aoe, K. Okamura, T. Date, M. Shibasaki, A New Multifunctional Heterobimetallic Asymmetric Catalyst for Michael Additions and Tandem Michael-Aldol Reactions, Angew. Chem. Int. Ed Engl 1996, 35,104-106. 

Third heterobimetallic asymmetric catalyst reported by Shibasaki et al., gallium-sodium-BINOL complex (GaSB) 26 and indium-potassium-BINOL complex (InPB), are also rather effective catalysts for asymmetric Michael reactions, and GaSB was better than InPB in terms of enantioselectivity. The GaSB catalyst was prepared from GaCl3, NaO Bu (4 mol equiv. to... 

Another advantage was conferred by introducing 6,6 -substituents to BINOL. In general, catalytic asymmetric syntheses of fluorine-containing compounds are rather difficult.42 However, an effective asymmetric nitroaldol reaction of the rather unreactive a,ct-difluoro aldehydes proceeded satisfactorily when using the heterobimetallic asymmetric catalysts generated from 6,6 -bis[(triethylsilyl)-ethynyl]BINOL, as shown in Table 5 43 The -configuration of the nitroaldol adduct 71 showed that the nitronate reacted preferentially on the Si face of the... 

The design for a direct catalytic asymmetric aldol reaction of aldehydes and unmodified ketones with bifunctional catalysts is shown in Figure 36. A Brpnsted basic functionality (OM) in the heterobimetallic asymmetric catalyst (I) could deprotonate the a-proton of a ketone to generate the metal enolate (II), while at the same time a Lewis acidic functionality (LA) could activate an aldehyde to give (III), which would then react with the metal enolate (in a chelation-controlled fashion) in an asymmetric environment to afford a P-keto metal alkoxide (IV). 

Inspired by enzyme chemistry, Shibasaki et al. [24] developed several heterobimetallic asymmetric catalysts [25], displaying both Lewis acidity and Br0nsted basicity. Best results so far were... 

An intramolecular diastereoselective Refor-matsky-type aldol approach was demonstrated by Taylor et al. [47] with an Sm(II)-mediated cy-clization of the chiral bromoacetate 60, resulting in lactone 61, also an intermediate in the synthesis of Schinzer s building block 7. The alcohol oxidation state at C5 in 61 avoided retro-reaction and at the same time was used for induction, with the absolute stereochemistry originating from enzymatic resolution (Scheme II). Direct re.solution of racemic C3 alcohol was also tried with an esterase adapted by directed evolution [48]. In other, somewhat more lengthy routes to CI-C6 building blocks, Shibasaki et al. used a catalytic asymmetric aldol reaction with heterobimetallic asymmetric catalysts [49], and Kalesse et al. used a Sharpless asymmetric epoxidation [50]. 

We speculated that it might be possible to develop a direct catalytic asymmetric aldol reaction of aldehydes and unmodified ketones by employing heterobimetallic catalysts. Our initial concerns were dominated by the possibility that our heterobimetallic asymmetric catalysts would be ineffective at promoting aldol reactions because... 

Ruck-Braun, K., Kunz, H. A new multifunctional heterobimetallic asymmetric catalyst for Michael additions and tandem Michael-aldol reactions. Chemtracts i997, 10, 519-521. 

In 1996, Shibasaki s group developed highly efficient bimetallic Al-M- / )-BINOL (M = Li, Na, K, or Ba) catalysts for asymmetric Michael reactions of malonic esters to enones, and excellent results were obtained (84-99% enantiomeric excess) (Table 19.1). Mechanistic studies on Al-Li-(/ )-BINOL ent-18 complex revealed that it worked as a multifunctional heterobimetallic asymmetric catalyst. 

Lanthanide-Alkali Metal Heterobimetallic Asymmetric Catalysts... 

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). 

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