DIPAMP rhodium complex

The rhodium complexes of the ferrocene derivatives 39 have shown useful characteristics for the reduction of itaconates as well as dehydroamino acid derivatives [15, 167-170]. These compounds are hybrids between ferrocene-based ligands and the various other types. The P-chiral compounds, which in some ways are DIPAMP hybrids, showed tolerance for the reduction of N-methyl en-amides to produce N-methyl-a-amino acid derivatives [169-171]. 

Although enol esters have a similar structure to enamides, they have proven more difficult substrates for asymmetric hydrogenation, which is evident from the significantly fewer number of examples. One possible explanation is the weaker coordinating ability of the enol ester to the metal center, as compared to the corresponding enamide. Some rhodium complexes associated with chiral phosphorous ligands such as DIPAMP [100, 101] and DuPhos [102] are effective for asymmetric hydrogenation of a-(acyloxy)acrylates. 

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... 

A number of groups have shown interest in the mechanism of asymmetric hydrogenation, principally of (a)-Z-acetamidocinnamic add and its derivatives. Kagan and co-workers have shown that cis addition of deuterium occurs to the Z isomer. Rhodium complexes of DIOP were used here. Koenig and Knowles obtained similar results with the ligands DIPAMP, cyclohexyl(o-... 

Introduction Catalytic hydrogenation with soluble catalysts Hydrogenation with C2-Symmetrical ftis-Phosphine Rhodium Complexes C2 symmetric ligands (DIPAMP, DIOP, PNNP)... 

Other metals can be similarly immobilised. Silica- and clay-supported rhodium complexes, for example, are effective hydrogenation catalysts.160,161 An interesting variant on this involves a heteropolyacid to assist the metal-support binding. The heteropolyadd, such as phosphotungstic add, is attached to the support (e.g. montmorillonite) by the indpient wetting technique. The solid material is then treated with a solution of the homogeneous catalyst such as Rh(DiPamp).162... 

N-acyldehydrodipeptides were readily prepared either by the condensation of N -acyldehydro-a-amino acids with a-amino acid esters or by the reaction of the azlactones of dehydro-a-amino acid with a-amino acid esters (eq. 1). Asymmetric hydrogenation of the N-acyldehydrodipeptides thus obtained (eq. 2) was carried out by using rhodium complexes with a variety of chiral diphosphines such as -Br-Phenyl-CAPP (3), Ph-CAPP (3), (-)BPPM (4), (+)BPPM (4), (-)DIOP ( ), (+)DIOP ( ), diPAMP (6), Chiraphos (7), Prophos (S), BPPFA (9) and CBZ-Phe-PPM (Fig. 1)(10). The chiral catalysts were prepared in situ from chiral diphosphine ligand with [Rh(NBD)2l -CIO4 (NBD = norbomadiene). Typical results are summarized in Tables I-V. 

Rhodium complexes of the type [(COD)Rh(DuPhos)]+X (X = weakly or noncoordinating anion) have been developed as one of the most general classes of catalyst precursors for efhcient, enantioselective low-pressure hydrogenation of enamides (21) (Scheme 9.22). ° The DuPhos approach overcomes some of the limitations of the DIPAMP system as the substrates may be present as mixtures of E- and Z-geometric isomers. For substrates that possess a single p-substituent (e.g., = H), the Me-DuPhos-Rh and Et-DuPhos-Rh catalysts were found to give enantioselec-... 

Variation of the ligands in the rhodium complex eventually led to the chiral phosphine DIPAMP. 

Figure 9.7 Rhodium complex of the chiral ligand DIPAMP [Rh(l,5-cyclo-octadiene = COD)DIPAMP] (tetrafluoroborate).

Two sets of data showed that the minor diastereomeric olefin complex generated the major enantiomer of the product. First, the structure of the major diastereomer of [Rh(S,S-CHIRAPHOS)(EAC)] was determined by single-crystal X-ray diffraction. The complex in this structure would form N-acetyl-(S)-phenylalanine ethyl ester, but tfie major enantiomer of the product was the (R)-isomer. Second, both diastereomers of the olefin complex were observed during the hydrogenation of MAC by the rhodium complex of (R,R)-DIPAMP. At temperatures low enough that these diastereomers do not interconvert, NMR studies showed that the minor diastereomer reacted much more rapidly with to form the reduced product than the major diastereomer. 

In the DIPAMP diphosphine, the two phosphorus atoms themselves are optically active. Rhodium DIPAMP complexes, discovered by Knowles (recipient of the Nobel Prize in 2001) (120,121), have been used by Monsanto for the commercial synthesis of (S)-3-(3,4-dihydroxyphenyl)alanine,(S)-DOPA, extensively used for the treatment of Parkinson s disease. Cationic rhodium complexes with these chiral diphosphines are very effective for the asymmetric hydrogenation of prochiral olefins, such as the interesting a-acetamidoacrylates, which can bind... 

Another fairly direct method for the synthesis of chiral amino acids involves the synthesis of a dehydroamino acid, 22.25, which is then hydrogenated in the presence of a chiral rhodium complex. The dehydroamino acid is prepared via an azlactone, with the full mechanism shown in Figure 22.21. The azlactone is then hydrolyzed to the dehydroamino acid. The dehydroamino acid derivative is readily reduced with a standard palladium catalyst, but the product is then racemic. If the catalyst used is [Rh(COD)(DIPAMP)] [BFJ, then the reaction proceeds with up to 99 % enantiomer excess (DIPAMP, 22.26). This is the basis of the Monsanto process for the production of the anti-Parkinson s drug, l-DOPA, 22.27, and William Knowles received the Nobel Prize for this work in 2001. 

In 1968, Knowles at Monsanto Company showed that a chiral transition metal based catalyst could transfer chirality to a nonchiral substrate resulting in a chiral product with one of the enantiomers in excess. The aim of Knowles was to develop an industrial synthesis process for the rare amino acid l-DOPA, which had proved useful in the treatment of Parkinson s disease. Knowles and co-workers at Monsanto discovered that a cationic rhodium complex containing DiPAMP (Fig. 2.5A), a chelating diphosphine with... 

The most effective catalysts for enantioselective amino acid synthesis are coordination complexes of rhodium(I) with 1,5-cyclooctadiene (COD) and a chiral diphosphine such as (JR,jR)-l,2-bis(o-anisylphenylphosphino)ethane, the so-called DiPAMP ligand. The complex owes its chirality to the presence of the trisubstituted phosphorus atoms (Section 9.12). 

An especially important case is the enantioselective hydrogenation of a-amidoacrylic acids, which leads to a-aminoacids.29 A particularly detailed study has been carried out on the mechanism of reduction of methyl Z-a-acetamidocinnamate by a rhodium catalyst with a chiral diphosphine ligand DIPAMP.30 It has been concluded that the reactant can bind reversibly to the catalyst to give either of two complexes. Addition of hydrogen at rhodium then leads to a reactive rhodium hydride and eventually to product. Interestingly, the addition of hydrogen occurs most rapidly in the minor isomeric complex, and the enantioselectivity is due to this kinetic preference. 

The hydrogenation reaction is carried out with a substituted cinnamic acid. The acetamido group is of particular importance because it functions as a secondary complexation function in addition to the alkene functionality. In the first step the alkene co-ordinates to the cationic rhodium species (containing an enantiopure phosphine DIPAMP in Figures 4.4 and 4.5 with the chirality at phosphorus carrying three different substituents, Ph, o-An, CH2) for which there are several diasteromeric structures due to ... 

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