Rh/dipamp

A Rh-dipamp complex was later applied by NSC Technologies for the manufacture of several unnatural amino acids with good catalyst performances (ee 95-98%, TON 5000-20000) [30] and was also very selective but with low activity (ee 98%, TON 20) in a feasibility study for a synthesis of acromelobic acid by Abbott Laboratories [31]. 

The preparation of this type of catalyst is quite simple. HPAs such as phos-photungstic acid were adsorbed onto inorganic supports such as clays, alumina, and active carbon. Subsequently, the metal complex was added to form the immobilized catalyst. If necessary, the catalyst can be pre-reduced. These types of catalysts were developed mainly for enantioselective hydrogenations. For instance, a supported chiral catalyst that was based on a cationic Rh(DIPAMP) complex, phosphotungstic acid and alumina showed an ee-value of 93% with a TOF of about 100 IT1 in the hydrogenation of 2-acetamidoacrylic acid methyl ester (Fig. 42.4 Table 42.2). 

Fig.44.9 31P,103Rh nH HMQC NMR spectrum of a methanolic solution of [Rh(DIPAMP)]+ solvent complex (0.01 mmol), which was treated with 1 mmol 1148 ppm (substrate complex). methyl-(Z)-/ -(N-acetyl)-aminocrotonate and... 

Chapter 2 to 6 have introduced a variety of reactions such as asymmetric C-C bond formations (Chapters 2, 3, and 5), asymmetric oxidation reactions (Chapter 4), and asymmetric reduction reactions (Chapter 6). Such asymmetric reactions have been applied in several industrial processes, such as the asymmetric synthesis of l-DOPA, a drug for the treatment of Parkinson s disease, via Rh(DIPAMP)-catalyzed hydrogenation (Monsanto) the asymmetric synthesis of the cyclopropane component of cilastatin using a copper complex-catalyzed asymmetric cyclopropanation reaction (Sumitomo) and the industrial synthesis of menthol and citronellal through asymmetric isomerization of enamines and asymmetric hydrogenation reactions (Takasago). Now, the side chain of taxol can also be synthesized by several asymmetric approaches. 

Figure 1.28 NMR spectra obtained after saturation transfer of the P nucieus trans to amide in the [Rh(dipamp)(enamide)] diastereoisomer 103a. Direct exchange of magnetisation is observed between the atoms trans to amide in the diastereomers 103a and 103b. The arrows pointing upwards indicate the most affected resonance. The proposed mechanism of intramolecular equilibration of 103a and 103b is shown.

Experimental investigations by Halpern and Landis on the hydrogenation of methyl-(Z)-a-acetamidocinnamate by Rh(DiPAMP) allowed them to propose the reaction mechanism discussed above. These studies also showed that minor changes on the substrate can drastically modify the enantiomeric excess. They found that enantiomeric excess depends on (i) the nature of the alkene substituents, and (ii) their relative positions (E or Z) the best re-... 

The substrate requirements have been rationalized for Rh(dipamp) reductions. Thus, for an enamine they can be divided into four specific regions (Figure 2.1)47 This has allowed the system to be used with confidence to prepare a wide variety of unnatural amino acids.39... 

The chemistry of Rh(DIPAMP) and mechanism has been reviewed.914 1617 2 28 Marginally higher catalyst efficiencies are observed with higher alcohols compared to methanol, whereas the presence of water can result in the reduction of slurries. Filtration of the product can improve the % ee while the catalyst and D,L-product remain in the mother liquor. The catalyst stereoselectivities decrease as hydrogen pressure increases. [Rh(COD)(R,W-DIPAMP) +BF4 (13) affords the. S -con-figuration of amino acids on reduction of the enamide substrate. Reduction of enamides in the presence of base eliminates the pressure variances on the stereoselectivities, but the rate of reaction under these conditions is slow.17... 

The advantages and disadvantages of Rh(DIPAMP) are summarized in Table 12.1. The catalyst precursor, 13, is air-stable, which simplifies handling operations on a manufacturing scale. Despite these advantages, ligand synthesis is very difficult. After the initial preparation of menthylmethyl-phenylphosphinate (16), the (/f),-isomer is separated by two fractional crystallizations (Scheme... 

Rhodium catalysts that contain 10a have been reported for the industrial preparation of L-dopa (,cf Scheme 12.1). Similar to the Monsanto Rh(DIPAMP) process, the enamide 14a has been reduced with [Rh(COD)(10a)]+BF4 in >90% ee by VEB Isis-Chemie Zwickau.90... 

Laneman, S. A., Froen, D. E., Ager, D. J. The Preparation of Amino Acids via Rh(DIPAMP)-Catalyzed Asymmetric Hydrogenations. In Catalysis of Organic Reactions, Herkes, F. E. Ed., Marcel Dekker New York, 1998, p. 525. 

Fig. 6.21. Synthesis of L-DOPA with the cationic Rh-DiPAMP catalyst.

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