Poisoning, chiral

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... 

Another interesting issue is the possibility of creating optically active compounds with racemic catalysts. The term chiral poisoning has been coined for the situation where a chiral substance deactivates one enantiomer of a racemic catalyst. Enantiomerically pure (R,R)-chiraphos rhodium complex affords the (iS )-methylsuccinate in more than 98% ee when applied in the asymmetric hydrogenation of a substrate itaconate.109 An economical and convenient method... 

In contrast to chiral poisoning, the concept of chiral activation has also emerged recently. An additional activator selectively or preferentially activates one enantiomer of the racemic catalyst, resulting in much faster reaction, and gives products with high ee. 

Enantiomer-selective deactivation of racemic catalyts by a chiral deactivator affects the enantiomer-selective formation of a deactivated catalyst with low catalytic activity (Scheme 8.2). Therefore, it is crucial for a chiral deactivator to interact with one enantiomer of a racemic catalyst (Scheme 8.2a). As the chiral deactivator does not interact with the other enantiomer of racemic catalyst, the enantiomeri-cally enriched product can be obtained. Therefore, the level of enantiomeric excess (% ee) could not exceed that attained by the enantiopure catalyst. On the other hand, nonselective complexation of a chiral deactivator would equally and simultaneously deactivate both catalyst enantiomers, thereby yielding a racemic product (Scheme 8.2b). Although this strategy tends to use excess chiral poison relative to the amount of catalyst, it offers a significant advantage in reducing cost and synthetic difficulty since readily available racemic catalysts and often inexpensive chiral poisons are used. 

The term chiral poisoning as a deactivating strategy has been proposed for the asymmetric hydrogenation reaction of dimethyl itaconate catalyzed by CHIRAPHOS-Rh complex (Scheme 8.5). The combination of racemic CHIRAPHOS-Rh complex and (5)-METHOPHOS 6 as a catalyst poison yields the hydrogenated product in 49% ee. (5)-METHOPHOS is believed to bind to the (S. S -CHlRAPHOS-Rh complex preferentially, as the use of enantiopure (R,R)-CHlRAPHOS-Rh complex affords the product with 98% ee. 

Enantiomerically pure diisopropyl D-tartrate (d-DIPT) can be used effectively as a chiral poison for racemic BINOLato-Ti(0 Pr)2- catalyzed addition of allyltributyl-tin to aldehydes (Scheme 8.7). The enantioselectivity of the product increases with an increase in the amount of d-DIPT employed. When Ti(0 Pr)4 and d-DIPT are employed in the ratio of 1 3, the enantioselectivity and yield of the homoallylic alcohol product increase to 91 % ee and 63% from 19% ee and 44% in a ratio of 1 1. 

As an excellent chiral poison for BINAPs-RuCl2(dmQ 7, 3,3 -dimethyl-2,2 -dia-mino-1,1 -binaphthyl (DM-DABN) has been designed in which methyl groups in (/ )-2,2 -diamino-1,1 -binaphthyl (DABN) would interact with equatorial Ar groups in (R)-BINAP but not in (S)-BINAP (Figure 8.1). 

Complete enantiomer discrimination and asymmetric deactivation of the racemic XylBINAP-RuCl2(dmf) ( )-7b using DM-DABN as a chiral poison are shown to be effective in the kinetic resolution of 2-cyclohexenol (Scheme 8.9). Use of just a 0.5 molar amount of (5)-DM-DABN relative to ( )-7b gives enantiopure (S)-2-cyclohexenol, which is kinetically resolved in the same conversion as enantiopure 7b. Indeed, the relative rate of hydrogenation of (R)- versus (5)-2-cyclohexenol in the presence of only a 0.5 molar amount of (5)-DM-DABN relative to ( )-7b is significantly large (kf/kg = 102). The combination of ( )-7b with (S)-DM-DABN also gives 99.3% ee of (R)-methyl 3-hydroxybutanoate quantitatively... 

The use of an activation/deactivation protocol with a chiral poison, (R)-DM-DABN (148), has been achieved with ruthenium catalysts that contained rac-xyl-BINAP and rac-tol-BINAP with chiral diamine (S,S)-DPEN. Asymmetric hydrogenation of 2-napthyl methyl ketone (128, Ar = 2-Naph, R = Me) without 148 gave the alcohol with 41% ee, whereas an enantioselectivity of 91% ee is obtained with deactivator 148 present (Scheme 12.58).197... 

VII. Asymmetric amplification in chiral poisoning or chiral activation of a racemic catalyst... 

VII. ASYMMETRIC AMPLIFICATION IN CHIRAL POISONING OR CHIRAL ACTIVATION OF A RACEMIC CATALYST... 

A chiral poison will destroy part of the racemic ligand or catalyst, in situ, by kinetic resolution. The remaining enantioenriched material will then act as the chiral catalyst. Chiral activation of a catalyst, on the other hand, generates a new... 

These results demonstrate the power of the chiral poisoning strategy under the optimal conditions. Deviations form such ideal behavior can result from incomplete inhibition of one... 

Figure 10 Idealized chiral poisoning involves complete deactivation of one enantiomers of the racemic catalyst, Cat( r) in this example, by the resolved poison...

Table 3 Comparison of the chiral poisoning strategy to the traditional use of chiral resolved BINAP derivative...

Faller demonstrated the enantiomer-selective deactivation of racemic BINOL-Ti complex by using DIPT-derived titanium complex as a chiral poison (vide infra) (Sch. 10) [44], The enantiomeric excess (ee) of the allylation product increased as the amount of DIPT employed was increased. 

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