Rh-Catalyzed Asymmetric Hydrogenation Reactions

Enamide hydrogenations have become a routine test reaction for evaluation of the effectiveness of new chiral Hgands [5,11,20,56,59,104]. In addition to being a test reaction, it stands as one of the most powerful and economic methods for the production of enantiomerically pure a-amino acid derivatives. Our group 

The X-ray crystallographic analysis of the unsymmetrical BisP shows a strong distortion of the five-membered chelation ring as compared to that of symmetric BisP [32]. The large difference in the steric repulsions between the bulky substituent borne on one phosphorus atom and the neighboring atoms on the one hand and the other (different) bulky substituent borne on the other phosphorus atom and the same neighboring atoms on the other hand is believed to be responsible for better steric matching with some substrates. 

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Scheme 22. Examples of Rh-catalyzed asymmetric hydrogenation reactions of dehydroammo esters...

Scheme 25. Rh-catalyzed asymmetric hydrogenation reactions leading to a biologically active compound...

Scheme 27. Example of the Rh-catalyzed asymmetric hydrogenation reaction of ethenephosphonate...

Selected derivatives of the ligands and complexes described above have been tested in catalytic applications. Early tests with bidentate P,P or P,N ligands such as 4, 6, and 8 in Rh-catalyzed asymmetric hydrogenation were disappointing, with ee values below 20%. However, as was demonstrated mainly by the Fu group, phosphaferrocene derivatives do have the potential for successful applications in asymmetric catalytic reactions, provided the phosphaferrocene is endowed with sufficient steric bulk. Examples are depicted in Eig. 1.5.8 the Cp derivative 32,... 

The new ligands were evaluated in the Rh-catalyzed asymmetric hydrogenation of benchmark substrates methyl a-N-acetamidoacrylate (7), methyl a-(2)-N-acetamidocinnamate (8) and dimethyl itaconate (9) (Table 2.3). For all three substrates, catalyst performance was superior in CH2CI2. Differences of up to 83% ee compared to otherwise identical reactions conducted in MeOH could be noted, giving... 

K. Rossen, Ru- and Rh-Catalyzed Asymmetric Hydrogenations Recent Surprises from an Old Reaction, Angew. Chem. Int. Ed. Engl. 2001, 40, 4611 4613. 

Although the Rh-catalyzed asymmetric hydrogenations of prochiral enamides have been extensively studied and excellent results have been frequently achieved, the catalytic asymmetric hydrogenations of 2-arylacrylic acids have been less successful. Until recently most catalyst systems gave only moderate optical yields for the 2-arylpropionic acid products (77). An important breakthrough in the study of these reactions was reported by Noyori et al. By using Ru(BINAP)(OAc)2 as a catalyst precursor, these researchers obtained excellent optical yields in the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic acid (72). 

In the Rh catalyzed asymmetric hydrogenation of enamides, why can the mixed two different chiral monodentate phosphorus hgands improve the enantioselectivity of reaction in some cases ... 

BDPAB were consistently higher than those from the same reaction with Rh (R) BDPAB catalyst. Rh (R) Hg BDPAB catalyst was extremely effective in the Rh catalyzed asymmetric hydrogenation of a arylenamides, leading to various chiral a arylethylamine derivatives with excellent enantioselectivities (up to 99.0% ee). 

Reek et al.73 developed a new bicarbazolediol-74 (BICOL)-based, chiral monodentate phosphoramidite ligand, in which the Ai-sites in the bicarbazole skeleton permitted the easy introduction of metal centers. As a model reaction, the Rh-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate was evaluated. Using a ligand to rhodium ratio of 2.2, the enantioselectivity induced by the rhodium complex (Figure 10.7) was 93% at full conversion,... 

The C2-symmetric biferrocene 16 has been reported by Ito and co-workers to behave as a frans-spanning chelating ligand. The combination of C2-symmetry and trans coordination geometry is conceptually new in the field and bears promises for future development. TRAP (the abbreviation for this kind of compounds) affords high enantioselectivities in the Rh-catalyzed asymmetric Michael reaction of 2-cyanopropionates [17], the hydrosilylation of simple ketones [18], the hydrogenation of )3,/9-disubstituted A-acetylaminoacrylic acid... 

Attempts to improve the solubility and immobilization of chiral hydrogenation catalysts in ionic liquids were presented by Lee and coworkers [112]. They synthesized a chiral Rh-complex carrying the dicationic bisphosphine ligand depicted in Fig. 5.3-7. Immobilization of the tricationic complex in [BMIM][SbFe] showed better immobilization results in contact with iPrOH compared to the non-modified complex Me-BDPMI in the Rh-catalyzed asymmetric hydrogenation of N-acetylphenylethenamine (Scheme 5.3-11). The ionic catalyst solution was reused three times without loss of activity. In the fourth mn conversion decreased but high conversions could still be realized by increasing the reaction time. 

Dihydroboronium derivatives of t-Bu-BisP with different cotmter anions were prepared, as shown in Scheme 56. The reaction of BisP with BH2Br afforded the boronium salt 175 which possessed a bromide ion. The dihydroboronium derivative of (S,S)-l,2-bis(tert-butylmethylphosphino)ethane 175 (t-Bu-BisP ) was prepared by the reaction of t-Bu-BisP 174 with catecholborane and used as chiral diphosphine ligand precursor in Rh-catalyzed asymmetric hydrogenated of methyl (Z)-acetamidocinnamate to afford the hydrogenation product in up to 94% ee. Complexes of iron(III) and P-chiral phosphine oxides 176 are catalysts for the asymmetric Diels-Alder reaction of iV-acrylamide dienophiles [106]. 

The undesired hydrolysis of phosphoramidites can lead to an unexpected alteration of catalytic results. Thus, during Rh-catalyzed asymmetric hydrogenation of a-substituted ethenylphosphonic acid, by chance Ding and coworkers [40] observed the hydrolysis of the P-N bond with adventitious water (Scheme 2.134). The newly formed secondary phosphine oxides were more efficient than the parent phosphoramidite ligands in the respective catalytic reaction. When an equimolar amount of NHj was added to the reaction mixture before hydrogenation was started, the reaction did not occur. This clearly indicates that the phosphine oxide is formed from the phosphoramidite only in acidic media. 

The Rh-catalyzed asymmetric hydrogenation of prochiral p-A-acet-ylamino-vinylphosphonates (145) allowed preparation of chiral p-A-acet-ylaminoethyl-phosphonates (146) with excellent yields (up to 100%) and high enantioselectivities (up to 92% ee) (Scheme 48). The reaction was strongly dependent on the structure of a chiral bidentate phosphorus ligand (PL ) and the solvent employed (THF, CH2CI2). In several cases an inversion of the induced chirality was observed by using the corresponding E- or Z-isomeric substrates. 

Self-Supported MonoPhos/Rh(l)-Catalyzed Asymmetric Hydrogenation Reactions... 

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