Asymmetric Hydrogenation of Cinnamic Acid Derivatives

By this, foams remain stable up to 12 min at 70 °C and no coalescence occurs within this period. It has to be mentioned, however, that the range of solvents to be used for a microreactor test unit is limited as a stable foam has to be established. So far, this was only possible for aqueous solutions. 

These flows were guided into a wound delay tube for reaction with ethylene glycol/water (60/40 wt%) and hydrogen [156,163]. Efficient mass transfer in a kinetically controlled manner was achieved by the large specific gas-liquid interfaces of the foams of up to 50 000 m /m.  

The deviation in the enantiomeric excess (ee) was small and 90% of all data were within 40-48% ee [162]. A kinetic analysis was made by fitting the experimental data 

Benchmarked property of the g/l screening Mini batch Microflow 

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The asymmetric hydrogenation of cinnamic acid derivatives has been developed by Knowles at Monsanto [4], The synthesis of L-dopa (Figure 4.3), a drug for the treatment of Parkinson s disease, has been developed and is applied on an industrial scale. Knowles received the Nobel Prize for Chemistry in 2001 together with Noyori (see below, BINAP ) and Sharpless (asymmetric epoxidation). 

The first industrially interesting production of a chiral pharmaceutical with a chiral metal complex catalyst is the asymmetric hydrogenation of cinnamic acid derivatives to give L-DOPA, see Fig. 6.21. 

Table 5 Asymmetric hydrogenation of cinnamic and tiglic acid derivatives...

Enzymatic hydrogenations generate optically pure isomers attempts to initiate such processes are made on metal-catalyzed hydrogenations. Asymmetric hydrogenation can fill the need for asymmetric compounds of which only one enantiomorph is active, e.g., amino acids such as L-lysine, 1 (indispensable in animal feeds), L-phenylalanine, 2 (a sweet peptide component), L-dopa 3 (a drug for Parkinsonism), are required in the L-form for human or animal consumption. Consequently, most of the examples investigated are related to the asymmetric hydrogenation of acrylic acid or cinnamic acid derivatives. 

NMR spectroscopy has been used to study the species formed in solution by interaction of cinnamic acid derivatives with asymmetric hydrogenation catalysts. Such studies are necessarily limited to those species which accumulate in adequate concentration and have sufficiently long lifetimes for observation by NMR. In catalytic reactions as rapid as those described here, such complexes appear likely to be outside rather than in the operating catalytic cycle. ... 

In recent years, the catalytic asymmetric hydrogenation of a-acylamino acrylic or cinnamic acid derivatives has been widely investigated as a method for preparing chiral a-amino acids, and considerable efforts have been devoted for developing new chiral ligands and complexes to this end. In this context, simple chiral phosphinous amides as well as chiral bis(aminophosphanes) have found notorious applications as ligands in Rh(I) complexes, which have been used in the asymmetric hydrogenation of a-acylamino acrylic acid derivatives (Scheme 43). 

Houpis, I.N., Patterson, L.E., Alt, C.A., Rizzo, J.R., Zhang, T.Y. and Haurez, M. S3mthesis of PPAR Agonist via Asymmetric Hydrogenation of a Cinnamic Acid derivative and Stereo-specific Displacement of (S)-2-Chloropropionic Acid. Org. Lett. 2005, 7, 1947-1950. 

Table I. Optical Yields for the Asymmetric Hydrogenation of a-(Acylamido)cinnamic Acid Derivatives Using Rhodium(I) Complexes Containing (NmenHCeHsJPC C P eHs ...

In the laboratory of D. Ma, the asymmetric synthesis of several metabotropic glutamate receptor antagonists derived from a-alkylated phenylglycines was undertaken. The preparation of (S)-1-aminoindan-1,5-dicarboxylic acid (AIDA) started with the Perkin reaction of 3-bromobenzaldehyde and malonic acid. The resulting ( )-cinnamic acid derivative was hydrogenated and the following intramolecular Friedel-Crafts acylation afforded the corresponding indanone, which was then converted to (S)-AIDA. 

Asymmetric Hydrogenation.—The asymmetric hydrogenation of a-acylamino-acrylates and cinnamates using chiral rhodium(i) diphosphine complexes as catalysts is now established as one of the best methods for obtaining optically pure a-amino-acids (see previous reviews in this series). In the past year, some new chiral diphosphines have been added to the already considerable number of such ligands. A bis(diphenylphosphino)-derivative of pyrrolidine in conjunction with Rh can be used to hydrogenate a-acetamidocinnamates and itaconic acid with chiral inductions of 90%, whereas an Rh -diphos complex derived from natural tartaric acid effects the reduction of some a-acylaminoacrylic acids to natural (5)-a-acylamino-acids with optical yields of between 80 and 100%. ... 

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