Binol asymmetric activator

A similar enantiomer-selective activation has been observed for aldol " and hetero-Diels-Alder reactions.Asymmetric activation of (R)-9 by (/f)-BINOL is also effective in giving higher enantioselectivity (97% ee) than those by the parent (R)-9 (91% ee) in the aldol reaction of silyl enol ethers (Scheme 8.12a). Asymmetric activation of R)-9 by (/f)-BINOL is the key to provide higher enantioselectivity (84% ee) than those obtained by (R)-9 (5% ee) in the hetero-Diels-Alder reaction with Danishefsky s diene (Scheme 8.12b). Activation with (/ )-6-Br-BINOL gives lower yield (25%) and enantioselectivity (43% ee) than the one using (/f)-BINOL (50%, 84% ee). One can see that not only steric but also electronic factors are important in a chiral activator. 

The advantage of asymmetric activation of the racemic BINOL-Ti(OPr )2 complex ( 2) is highlighted in a catalytic version (Table 8C.3, entry 5) wherein high enantioselectivity (80.0% ee) is obtained by adding less than the stoichiometric amount (0.25 molar amount) of (R)-BI-NOL [42a], A similar phenomenon has been observed in the aldol [42c] and (hetero) Diels-Al-der [44] reactions catalyzed by the racemic BINOL-Ti(OPr )2 catalyst (+2). 

Figure 8C.5. Kinetic feature of asymmetric activation of BINOL-Ti (OPr >2-...

Table 3. Asymmetric activation of enantio-pure (f )-BINOL- Ti(OPr )2 (2).

In the Diels-Alder reaction of glyoxylates with the Danishefsky diene (Sch. 53), asymmetric activation of (f )-BINOL-Ti(OPr )2 (2) by (/ )-BINOL is essential if enantioselectivity is to be higher than that achieved by use of the enantio-pure BINOL-Ti catalyst (5 % ee) [78], Effects of the torsional angles of 2,2 -biaryldiol ligands have been examined in the asymmetric Diels-Alder reaction of acrylate catalyzed by titanium complexes [133]. 

Asymmetric activation of chiral BINOL zirconium catalyst was reported as shown in Equation 37 [42]. Addition of optically active naphthyl alcohol (81) to the asymmetric allylation of benzaldehyde with allyltributyltin in the presence of catalyst (80) improved the enantioselectivity of optically active homoallyl alcohol (82) compared with the reaction without activator (81). 

Asymmetric Activation. The catalyst efficiency and enantioselectivity of BINOL-Ti complexes can be further increased throu asymmetric activation (42-45). Thus, the (/ )-6,6 -Br2-BINOL-Ti(OPf)2, prepared from Ti(OPr )4 and (R)-6,6 -Br2-BINOL, was activated by the addition of acidic activators such as (R)-5-Cl-BIPOL and (/ )-6,6 -Br2-BINOL (Table II). In all runs, chemical yields were obviously improved by the addition of acidic activators, in sharp contrast to the same reaction catalyzed by Yb(OTf)3, in which the addition of (/ )-6,6 -Br2-BINOL obviously decreases the catalytic activity 10 mol% Yb(OTf)3 wiAout (/ )-6,6 -Br2-BINOL 78% (paralortho = 7), the addition of (i )-6,6 Br2-BINOL (1 eq) 42% (paralortho = 13), 2 eq 45% (para/ordto = 16). The more acidic catalyst was prepared by the coordination of the acidic 6,6 -Br2-BINOL with the (/ )-6,6 -Br2-BINOL-Ti(OPr )2, in particular (42,43). In combination with a matched chiral activator, the enantioselectivity can be improved up to 90% ee as well as producing a high chemical yield (runs 6, 7). 

Table II The F-C reactions of aromatic compounds with fluoral catalyzed by (i )-6,6 -Bn-BINOL-Ti complex through asymmetric activation.

Over the last few years several examples have been reported in the field of asymmetric catalysis that are based on the interaction of two centers.6,119 Recently, Shibasaki and coworkers have developed an asymmetric two-center catalyst. Scheme 3.14 shows preparation of optically active La binaphthol (BINOL). This catalyst is effective in inducing the asymmetric nitro-aldol reaction, as shown in Scheme 3.15. 

Two reports have been made of the preparation of P-chiral phosphine oxides through reaction of chiral f-butylphenylphosphine oxide treated with LDA and electrophiles. The electrophiles included aldehydes,355 ketones,355 and benzylic-type halides.356 Optically active a-hydroxyphosphonate products have also been generated from aldehydes and dialkyl phosphites using an asymmetric induction approach with LiAl-BINOL.357... 

Catalytic asymmetric cyanide addition to imines constitutes an important C—C bondforming reaction, as the product amino nitriles may be converted to non-proteogenic a-amino acids. Kobayashi and co-workers have developed two different versions of the Zr-catalyzed amino nitrile synthesis [73]. The first variant is summarized in Scheme 6.22. The bimetallic complex 65, formed from two molecules of 6-Br-binol and one molecule of 2-Br-binol in the presence of two molecules of Zr(OtBu)4 and N-methylimidazole, was proposed as the active catalytic species. This hypothesis was based on various NMR studies more rigorous kinetic data are not as yet available. Nonetheless, as depicted in Scheme 6.22, reaction of o-hydroxyl imine 66 with 5 mol% 65 and 1—1.5 equiv. Bu3SnCN (CH2C12, —45 °C) leads to the formation of amino nitrile 67 with 91 % ee and in 92 % isolated yield. As is also shown in Scheme 6.22, electron-withdrawing (— 68) and electron-rich (—> 69), as well as more sterically hindered aryl substituents (— 70) readily undergo asymmetric cyanide addition. 

H. Sasai, T. Suzuki, N. Itoh, K. Tanaka, T. Date, K. Oka-mura, M Shibasaki, Catalytic Asymmetric Nitroaldol Reaction Using Optically Active Rare Earth BINOL Complex Investigation of the Catalyst Structure, J. Am Chem Soc 1993,115,10372-10373. 

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