Asymmetric deactivation

Entry ( )-8 (equiv) P (equiv) Time (h) Conv. (%) % de (exo endo) % ee (Config.) 

L-proline and L-prolinamide, respectively. In both cases, the remaining (/ ru,5)-8 is free to catalyze the asymmetric Diels-Alder reaction. 

2 Asymmetric Activation of Chiraiiy Rigid (Atropos) Cataiysts 

Ene reactions catalyzed by enantiopure (R)-9 can also be achieved with (7 )-BINOL as a chiral activator (Table 8.3). The reaction proceeds to give higher chemical yield (82.1 %) and enantioselectivity (96.8% ee) than those attained without the additional BINOL activator (19.8%, 94.5% ee) (entry 1 vs. 2). Kinetic studies indicate that the reaction catalyzed by (/f)-BESfOLato-Ti(0 Pr)2/(/f)-BESfOL complex ((/f,/ act)-9) is 25.6 times as fast as that catalyzed by (R)-9. These results imply that ( )-9 and a half-molar amount of (/f)-BINOL complex give (/f,/ act)-9, leaving (S)-9 uncomplexed. In contrast, (5)-BINOL activates (R)-9 to a smaller degree (entry 3), giving lower optical (86.0% ee) and chemical (48.0%) yields than with (K)-BINOL. 

Entry Catalyst Ketone Temp. ( C) Time (h) Yield (%) ee (%) 

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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... 

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... 

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). 

As described in the preceding sections, asymmetric amplification is generally a consequence of the formation of aggregates (i.e., dimers or oligomers that are homochiral or heterochiral) of a chiral catalyst. However, even a racemic catalyst can be used as a chiral catalyst with the aid of chiral additives (a simple model consisting of dimers is depicted in Scheme 9.17). If a chiral additive (R)-B is selectively associated with (S)-A in the racemic catalyst, the remaining (R)-A could operate as the chiral monomer catalyst (asymmetric deactivation). Conversely, the chiral additive (/ )-B can be selectively associated with (/ )-A in racemic catalyst to generate an active dimeric catalyst (asymmetric activation). 

Based on the concept mentioned above, Brown realized the asymmetric deactivation of a racemic catalyst in asymmetric hydrogenation (Scheme 9.18) [35]. One enantiomer of (+)-CHIRAPHOS 28 was selectively converted into an inactive complex 30 with a chiral iridium complex 29, whereas the remaining enantiomer of CHIRAPHOS forms a chiral rhodium complex 31 that acts as the chiral catalyst for the enantioselective hydrogenation of dehydroamino acid derivative 32 to give an enantio-enriched phenylalanine derivative... 

Catalyst Decay. Asymmetric hydrogenation of the SM using the Et-DuPhos-Rh catalyst exhibits a catalyst threshold behavior. When the initial charge of the catalyst is below this threshold value, the reaction is not completed. This indicates that the catalyst may become deactivated. 

The isolation of product is usually possible after evaporation of the solvent and extraction with hexane, ether, or toluene. Supported versions, for example on polystyrene grafted with PPh2 groups, have proved unsatisfactory because the rate of deactivation is greatly enhanced under these conditions [37]. Asymmetric versions exist, but the ee-values tend to be lower than in the Rh series [38]. With acid to neutralize the basic N lone pair, imine reduction is fast. Should it be necessary to remove the catalyst from solutions in order to isolate a strictly metal-free product, a resin containing a thiol group should prove satisfactory. A thiol group in the substrate deactivates the catalyst, however. 

The effects of added C02 on mass transfer properties and solubility were assessed in some detail for the catalytic asymmetric hydrogenation of 2-(6 -meth-oxy-2 -naphthyl) acrylic acid to (Sj-naproxen using Ru-(S)-BINAP-type catalysts in methanolic solution. The catalytic studies showed that a higher reaction rate was observed under a total C02/H2 pressure of ca. 100 bar (pH2 = 50bar) than under a pressure of 50 bar H2 alone. Upon further increase of the C02 pressure, the catalyst could be precipitated and solvent and product were removed, at least partly by supercritical extraction. Unfortunately, attempts to re-use the catalyst were hampered by its deactivation during the recycling process [11]. 

The 4 A Molecular Sieves System. The initial procedure for the Sharpless reaction required a stoichiometric amount of the tartrate Ti complex promoter. In the presence of 4 A molecular sieves, the asymmetric reaction can be achieved with a catalytic amount of titanium tetraisopropoxide and DET (Table 4-2).15 This can be explained by the fact that the molecular sieves may remove the co-existing water in the reaction system and thus avoid catalyst deactivation. Similar results may be observed in kinetic resolution (Table 4-3).15... 

In addition to the asymmetric conjugate addition involving an enone substrate and a relatively inactive nucleophile, there exists another kind of reaction in which a deactivated substrate and a normal nucleophile are involved. For example, under proper conditions, ordinary organometallic compounds such as... 

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... 

Asymmetric carbometalation has proved less successful with the [(EBTHI)ZrCl2] catalyst this may be due to deactivation of the catalytically active cationic species by the formation of a rather stable p-AlMe3 adduct, which does not occur with the [(NMI)2ZrCl2] catalyst system [75]. 

Photodimerization of cinnamic acids and its derivatives generally proceeds with high efficiency in the crystal (176), but very inefficiently in fluid phases (177). This low efficiency in the latter phases is apparently due to the rapid deactivation of excited monomers in such phases. However, in systems in which pairs of molecules are constrained so that potentially reactive double bonds are close to one another, the reaction may proceed in reasonable yield even in fluid and disordered states. The major practical application has been for production of photoresists, that is, insoluble photoformed polymers used for image-transfer systems (printed circuits, lithography, etc.) (178). Another application, of more interest here, is the use that has been made of mono- and dicinnamates for asymmetric synthesis (179), in studies of molecular association (180), and in the mapping of the geometry of complex molecules in fluid phases (181). In all of these it is tacitly assumed that there is quasi-topochemical control in other words, that the stereochemistry of the cyclobutane dimer is related to the prereaction geometry of the monomers in the same way as for the solid-state processes. 

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