Asymmetric activations

These new generation catalysts have been applied to the asymmetric activation of an inactive racemic metal compound by a non-racemic enantiopure ligand, called a vitamer (Scheme 20a). In contrast, a racemic catalyst can interact with an enantiopure chiral poison (asymmetric... 

The best combination turned out to be L5 /A9 (ee = 90% at room temperature and 99% at —78 °C with benzaldehydes and ee = 92-99% with other aldehydes).87 Further improvements were reported later.89 Although only a few dozen reactions were monitored by a JASCO-CD-995 instrument, the CD-based assay is amenable to high-throughput screening of enantioselective catalysts. The chemistry itself lends itself ideally to combinatorial asymmetric metal catalysis, since the principle of asymmetric activation is turning out to be very powerful.89... 

Fig. 32.49 Hydrogenation of ketones catalyzed by racemic BINAP-Ru complexes and (S,S)-DPEN asymmetric activation.

For aqueous solutions of salts, lt, (P, 7) represents the chemical potential of pure ions. This chemical potential cannot be measnred experimentally. Instead of nsing this hypothetical standard state, the activity coefficients of ions often are normalized by introducing the asymmetrical activity coefficient, y,, defined as... 

We first present some representative results via catalytic asymmetric activation of C—H and C C bonds in organic synthesis. In the next section, we will summarize the representative strategies, substrates, and chiral hgands that are used in asymmetric activation of C—H and C—C bonds. More detailed discussions and related results, can be found in the references cited. 

Asymmetric activation of the C—H bonds in benzyl silyl ethers was achieved by using Hashimoto s A-phthaloyl-based Rh2((5)-PTTL)4 catalyst (Figure 5.6) in high diastereoselectivities and enantioselectivities (Scheme 5.15). The well-established dirhodium tetraprolinates such as Rh2((5)-DOSP)4 and Rh2((R)-DOSP)4 catalysts, which generally are excellent catalysts for asymmetric C—H bond activation, were not suitable catalysts in these reactions. 

In contrast to the asymmetric activation of C—H bonds in benzyl silyl ethers, the dirhodium tetraprolinate, Rh2(5-DOSP)2 (Figure 5.7), was found to be an efficient catalyst in an enantioselective C—H activation of acetals (Scheme 5.16). Interestingly, when the acetals had a methoxy substituent on the aromatic ring, the Stevens rearrangement was a main competing side reaction of the C—H activation of acetals. 

Scheme 5.15. Asymmetric activation of C—H bonds in benzyl silyl ethers.

Asymmetric Activation of Chiraiiy Rigid (Atropos) Cataiysts... 

In contrast to asymmetric deactivation, Mikami has reported a conceptually opposite strategy, asymmetric activation. A highly activated chiral catalyst can be produced by addition of a chiral activator (Scheme 8.11). This strategy has the advantage that the activated catalyst can afford products with a higher enantiomeric... 

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. 

ASYMMETRIC ACTIVATION AND DEACTIVATION OF RACEMIC CATALYSTS (a) Aldol reaction... 

Asymmetric Activation/Deactivation of Chirally Rigid (Atropos) Catalysts... 

Combination of the asymmetric activation and asymmetric deactivation protocols as asymmetric activation/deactivation can be achieve the difference in catalytic activity between the two enantiomers of racemic catalysts can be maximized through selective activation and deactivation of enantiomeric catalyst, respectively (Scheme 8.15). 

The asymmetric activation can be done by a chiral activator through in situ diastereomer interconversion of the tropos ligand of racemic catalysts (Scheme 8.22). One possible case is that selective complexation of a chiral activator with one enantiomer of a racemic catalyst occurs. The remaining enantiomeric catalyst may then isomerize and complex with the chiral activator leading to a single diastereomer (Scheme 8.22a). The other case is that nonselective complexation of a tropos catalyst with a chiral activator initially provides a 1 1 ratio of activated diastereomers, which would isomerize to the single diastereomeric activated complex (Scheme 8.22b). 

The dynamic asymmetric activation can be rationalized by a continuum from the nonselective to selective complexation with a chiral activator. Figure 8.4 shows the difference in the relative rate ( rei = KcJKa ranges from 0.01 to 100) in the ratio of the diastereomeric catalysts (ranges from a 1 1 to 99 1) ... 

Davies, Renaud, and Sibi independently reported the chiral relay approach to control the enhanced steric extension inside a substrate to achieve increased asymmetric induction. However, as our study proves, the asymmetric activation of a tropos catalyst clearly differs from the chiral relay approach, in which substrate conformational control is utilized, since asymmetric activation controls the chiral environment of a tropos catalyst by the addition of a chiral external source (a chiral activator). 

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