Lithium binaphthoxides

According to the hypothetical catalytic cycle (Figure 36), the lanthanum atom is believed to function as a Lewis acid and a lithium binaphthoxide moiety as a Brpnsted base. The nature of the coordination of the aldehyde appears to be of first importance. This coordination provides activation of the aldehyde for reaction with the hypothetical LLB-enolate (II) (which on the basis of pKa values can be present at most in low concentration), and also controls of the orientation of the aldehyde for enantioselective reaction. A H NMR study also supports the existence of the coordination between aldehydes and the lanthanum cation.89... 

Bronsted base [the lithium binaphthoxides] and of a Lewis acid [La(UI)] sitting side by side at the heart of the LLB multifunctional catalyst evokes the active site of aldolases and probably explains why simple unmodified ketones and primary aldehydes can be used504. The examples in Scheme 132 illustrate the performance of this system612. 

A possible way to induce enantioselectivity in the aldol reaction is to empioy a chirai catalyst. M. Shibasaki and coworkers developed a bifunctional catalyst, (S)-LLB (L=lanthanum LB=lithium binaphthoxide), which could be successfully applied in direct catalytic asymmetric aldol reactions. An improved version of this catalyst derived from (S)-LLB by the addition of water and KOH was utilized in the formal total synthesis of fostriecin. ... 

Lanthanum catalysts were generated by Shibasaki and coworkers from lithium binaphthoxide and LaCl3 in the presence of NaOH and water [847, 848, 849], These reagents catalyze asymmetric nitroaldol reactions with a good enantioselec-tivity, but are less efficient in promoting asymmetric additions of dialkylphosphites to aldehydes [850],... 

LLB lanthanum-lithium-binaphthoxide complex LaLi3tris(binaphthoxide)... 

Therein, the lanthanum center ion (III) should function as a Lewis acid activating the aldehyde, whereas the lithium binaphthoxide moiety act as Bronsted base moiety. The synergetic effect of both groups, as can be seen in intermediate III, appeared to be responsible that the reaction proceeds without any activation of the starting materials, especially the ketone component. 

The bifunctional heterobimetalhc complexes developed by Shibasaki and coworkers, which have been used to effect high ees in a variety of conjugate additions discussed in this chapter, are also effective in the conjugate additions of hydroxylamines to enones and up to 99% ee has been obtained using the ytterbium lithium binaphthoxide YListrisjbinaphthoxide) (YLB). °... 

Quite a number of asymmetric thiol conjugate addition reactions are known [84], but previous examples of enantioselective thiol conjugate additions were based on the activation of thiol nucleophiles by use of chiral base catalysts such as amino alcohols [85], the lithium thiolate complex of amino bisether [86], and a lanthanide tris(binaphthoxide) [87]. No examples have been reported for the enantioselective thiol conjugate additions through the activation of acceptors by the aid of chiral Lewis acid catalysts. We therefore focussed on the potential of J ,J -DBFOX/ Ph aqua complex catalysts as highly tolerant chiral Lewis acid catalyst in thiol conjugate addition reactions. 

Without question, the most significant advance in the use of sulfur-centered nucleophiles was made by Shibasaki, who discovered that 10 mol% of a novel gallium-lithium-bis(binaphthoxide) complex 5 could catalyze the addition of tert-butylthiol to various cyclic and acyclic meso-epoxides with excellent enantioselectiv-ities and in good yields (Scheme 7.11) [21], This work builds on Shibasaki s broader studies of heterobimetallic complexes, in which dual activation of both the electrophile and the nucleophile is invoked [22]. This method has been applied to an efficient asymmetric synthesis of the prostaglandin core through an oxidation/ elimination sequence (Scheme 7.12). 

A similar [4 + 2] cyclization between 74 and CP was also conducted with a CH2CI2 solution of AlLi3tris(binaphthoxide) (75) [87, 88]. Catalyst 75 has a saturated coordination number with respect to the aluminum atom, which thus no longer has vacant orhitals for further complexation with other incoming Lewis bases. Whereas the ee of the adduct was very low (16 % ee), this result strongly suggests the possibility that lithium ions in 75 serve as Lewis acids in non-polar solvents. 

All the above-mentioned LnSB crystals showed similar mass patterns compared to those of Ln-Li-BINOL complexes, though they contained sodium instead of lithium. The oligomeric structure of the catalysts in the reaction mixture was supported by a slightly positive asymmetric amplification in the asymmetric nitroaldol reaction [9]. In addition, quite recently Shibasaki et al. reported the first X-ray crystallographic structure of a lithium-containing heterobime-tallic catalyst of type LnLB, namely the SmLi3tris(binaphthoxide) complex SmLB [8]. 

Later, Sasai et al. found that a combination of the heterobimetalhc complex boron-lithium-mono(binaphthoxide) (BLB) (380) and (Bu")3P is effective in promoting the enantioselective MBH reaction of cyclic enones with aldehydes via double activation to afford the adduct in good chemical yield with moderate to high enantioselectivity (Scheme 2.216) ... 

A highly efficient asymmetric cyanoetho ycarbonylation of aldehydes catalysed by heterometallic (S)-aluminium lithium bis(binaphthoxide) 18 and cinchonine was described by the Feng group in 2007 (Scheme 19.13). Under mild reaction conditions, excellent yields and enantioselectivities could be obtained for a variety of aldehydes. In particular, solid (S)-ALB-18... 

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... 

Direct Aldol Reactions The most frequently applied direct aldol reactions in which unmodified achiral methyl ketones can be directly activated by catalysts were reported by Trost [26] and Shibasaki [27] (Scheme 2.117). Both used bimetalUc catalysts as enzymatic numetics for ketone activation. Shibasaki reported the use of LuLi tris (binaphthoxide) to perform aldol reactions between methyl ketones and branched aldehydes. The underlying notion was that this catalyst mimics enzymatic activity through Lewis acid activity based on the lanthanum ion and Brpnsted basic activity due to the lithium binaphtoxide. The enantiomeric selectivity ranges from modest to excellent ratios. 

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. 

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