CHIRAPHOS hydrogenations

Recently, a series of chiral diphosphines (S. -Me-Duphos, (S. -chiraphos, (R,R)-diop and (+)-Norphos were grafted after an ionic exchange onto Al-MCM-41 134 complexes of the form [Rh(cod)(diphosphine)]+ were tested for the hydrogenation of dimethylitaconate. The supported complex with (S,S)-methyl-Duphos reached an activity for the formation of dimethyl ( -methyl-succinate as high as TON = 4000 with an ee close to 92%. Both (R,R)-diop and (,S S )-chiraphos give lower enantioselectivities (ee = 34% and 47% respectively). With (+)-Norphos, dimethyl-([Pg.457]

Remarkable success has been achieved by Fryzuk and Bosnich (247) using the complex [Rh(5,5-chiraphos)(COD)]+, where the chiral ligand 25,55-bis(diphenylphosphino)butane, a diphosphine chiral at carbons (25), is readily synthesized from 2R,3R-butane diol. TheZ-isomers of the prochiral a-N-acylaminoacrylic acid substrates were hydrogenated at ambient conditions to / -products with very high enantiomeric excess indeed, leucine and phenylalanine derivatives were obtained in complete optical purity. Catalytic deuteration was shown to lead to pure chiral f3-carbon centers as well as a-carbon centers in the leucine and phenylal-... 

Norton and coworkers found that catalytic enantioselective hydrogenation of the C=N bond of iminium cations can be accomplished using a series of Ru complexes with chiral diphosphine ligands such as Chiraphos and Norphos [68], Even tetra-alkyl-substituted iminium cations can be hydrogenated by this method. These reactions were carried out with 2 mol.% Ru catalyst and 3.4—3.8 bar H2 at room temperature in CH2C12 solvent (Eq. (39)). 

Rh complexes with ChiraPhos, PyrPhos, or ferrocenyl phosphines lacking amino alkyl side chains (such as BPPFA) are much less active toward tetrasubstituted olefins. Table 6-1 shows that in asymmetric hydrogenations catalyzed by 5a-d, the coordinated Rh complex exerts high selectivity on various substrates. It is postulated that the terminal amino group in the ligand forms an ammonium carboxylate with the olefinic substrates and attracts the substrate to the coordination site of the catalyst to facilitate the hydrogenation. 

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... 

The mechanism of hydrogenation of methyl (Z)-2-(acetamido)cinnamate catalyzed by a CHIRAPHOS- or DIPAMP-Rh complex have been exhaustively... 

Figure 1.3. Catalytic hydrogenation of A-acylated dehydroamino esters via an unsatu-rated/dihydride mechanism the p substituents in the substrates are omitted for clarity [P-P = (i ,R)-DIPAMP, (i ,i )-CHIRAPHOS, or (R)-BINAP S = solvent or a weak ligand].

A resolution of racemic CHIRAPHOS ligand has been achieved using a chiral iridium amide complex (Scheme 8.3). The chiral iridium complex (- -)-l reacts selectively with (S.S -CHIRAPHOS to form the inactive iridium complex 2. The remaining (R,R)-CHIRAPHOS affords the catalytically active chiral rhodium complex 3. The system catalyzes asymmetric hydrogenation to give the (5)-product with 87% ee. The opposite enantiomer (—)-l gives the (R)-product with 89.5% ee, which is almost the same level of enantioselectivity obtained by using optically pure (5,5)-CHlRAPHOS. 

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. 

Racemic diphosphines may be resolved by using transition metal complexes that contain optically active olefinic substrates (Scheme 11) (24). When racemic CHIRAPHOS is mixed with an enantiomerically pure Ir(I) complex that has two ( —)-menthyl (Z)-a-(acetam-ido)cinnamate ligands, (S,5)-CHIRAPHOS forms the Ir complex selectively and leaves the R,R enantiomer uncomplexed in solution. Addition of 0.8 equiv of [Rh(norbomadiene)2]BF4 forms a catalyst system for the enantioselective hydrogenation of methyl (Z)-a-(acetamido)cinnamate to produce the S amino ester with 87% ee. Use of the enantiomerically pure CHIRAPHOS-Rh complex produces the hydrogenation product in 90% ee. These data indicate that, in the solution containing both (S,S)-CHIRAPHOS-Ir and (/ ,/ )-CHIRAPHOS-Rh complexes, hydrogenation is catalyzed by the Rh complex only. 

Halpem and co-workers have carried out a detailed investigation of the mechanism of the asymmetric hydrogenation of methyl (MAC) and ethyl (EAC) (Z)-a-acetamidodnnamate by rhodium complexes of the ligands DIPAMP (50) and CHIRAPHOS (51).259 Coordination of alkene precedes the oxidative addition of hydrogen. For both ligands, one of the two possible diastereoisomers of the rhodium-diphosphine-alkene complex predominates in solution to a large extent. From the reaction of EAC with the S,S-CHIRAPHOS complex, this diastereoisomer has been isolated. Its structure is represented in (57).260... 

Halpern has shown that this predominant isomer exhibits negligible activity towards the oxidative addition of hydrogen. The minor isomer, which could be detected in solution for DIPAMP but not for CHIRAPHOS, reacts far more rapidly with hydrogen and is responsible for producing the major enantiomer of the hydrogenation product. The optical selectivity is thus due to this difference in reaction rates and not simply to the preferred manner of coordination of the alkene to the rhodium-diphosphine species.259,260 The precise reasons for this large difference in the rates of reaction of the two diastereoisomers with hydrogen are not yet known. The full mechanism is shown in Scheme 14. 

Efficient asymmetric hydrogenation of alkenes other than the amino acid and dipeptide precursors described above has met with only limited success. This appears to be at least in part due to the inability of many alkenes to function as bidentate chelates. Ethyl 2-acetoxyacrylate was hydrogenated with an enantiomer excess of 89% using [Rh(cod)(R,R-DIPAMP)]+, giving the S-enantiomer (equation 53). The ligands CHIRAPHOS, PROPHOS, DIOP, BPPM and CAMP were less effective.266... 

Unlike the Rh-based hydrogenation of a-(acylamino)acrylates, the corresponding Ru chemistry has not been studied extensively. Ru complexes of (S)-BINAP and (S,S)-CHIRAPHOS catalyze the hydrogenation of (Z)-a-(acylamino)cinnamates to give the protected ( -phenylalanine with 92% ee [74] and 97% ee [75], respectively. It is interesting that the Rh and Ru complexes with the same chiral diphosphines exhibit an opposite sense of asymmetric induction (Scheme 1.6) [13,15,56,74,75]. This condition is due primarily to the difference in the mechanisms the Rh-catalyzed hydrogenation proceeds via Rh dihydride species [76], whereas the Ru-catalyzed reaction takes place via Ru monohydride intermediate [77]. The Rh-catalyzed reaction has been studied in more detail by kinetic measurement [78], isotope tracer experiments [79], NMR studies [80], and MO calculations [81]. The stereochemical outcome is understandable by considering the thermodynamic stability and reactivity of the catalyst-enamide complexes. 

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... 

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