Amino acids ruthenium hydrogenation

Reductive alkylation by alcohol solvents may occur as an unwanted side reaction 22,39), and it is to avoid this reaction that Freifelder (20) recom mends ruthenium instead of nickel in pyridine hydrogenation. Alkylation by alcohols may occur with surprising ease 67). Reduction of 18 in ethanol over 10% palladium-on carbon to an amino acid, followed bycyclization with /V,/V-dicyclohexylcarbodiimide gave a mixture of 19 and 20 wiih the major product being the /V-ethyl derivative 49,50). By carrying out the reduction in acetic acid, 20 was obtained as the sole cyclized product 40). 

As expected initial examination of the hydrogenation of this substrate revealed its relatively low activity compared to dehydroamino acids that provide 3-aryl-a-amino acids. By carrying out the hydrogenation at an elevated temperature, however, the inherent low activity could be overcome. A screen of the Dowpharma catalyst collection at S/C 100 revealed that several rhodium catalysts provided good conversion and enantioselectivity while low activity and selectivity was observed with several ruthenium and iridium catalysts. Examination of rate data identified [(l )-PhanePhos Rh (COD)]Bp4 as the most active catalyst with a rate approximately... 

When we first contemplated thermochemical products available from Glu, a search of the literature revealed no studies expressly directed at hydrogenation to a specific product. Indeed, the major role that Glu plays in hydrogenation reactions is to act as an enantioselectivity enhancer (17,18). Glu (or a number of other optically active amino acids) is added to solutions containing Raney nickel, supported nickel, palladium, or ruthenium catalysts and forms stereoselective complexes on the catalyst surface, leading to enantioselective hydrogenation of keto-groups to optically active alcohols. Under the reaction conditions used, no hydrogenation of Glu takes place. 

An interesting application of TSIL was developed by Zhang et al for the catalytic hydrogenation of carbon dioxide to make formic acid. Ruthenium immobilized on silica was dispersed in aqueous IL solution for the reaction. H2 and CO2 were reacted to produce formic acid in high yield and selectivity. The catalyst could easily be separated from the reaction mixture by filtration and the reaction products and the IL were separated by simple distillation. The TSIL developed for this reaction system was basic with a tertiary amino group (N(CH3)2) on the cation l-(A,A-dimethylaminoethyl)-2,3-dimethylimidazolium trifluoromethanesulfonate, [mammim] [TfO]. 

Also, Klabunovskii reported pressure dependences of the OYs in enantio-differentiating hydrogenations of ethyl acetoacetate (EAA) with ruthenium (67), Raney cobalt (65), and RNi catalysts (69) modified with TA, c. Additives. Additives which are added to the reaction system often exert a remarkable effect on the OY of the enantio-differentiating hydrogenation of M A A (23-25). Water is one such additive. For example, in most hydrogenations with amino acid MRNis, the direction of differentiation was reversed by the addition of small amounts of water as shown in Fig. 14 (23, 25). 

Asymmetric catalysis has been most prevalent in the area of homogeneous hydrogenations. As previously stated, producing considerable amounts of a single enantiomer or diastereoisomer from a small amount of chiral catalyst has a huge industrial impact. Natural and unnatural amino acids, particularly L-dopa (12), have been produced by this method.17-21 Catalysts based on rhodium and ruthenium have enjoyed the most success. 

With ferrocenyl diamines such as 32, the transfer hydrogenation of I -acetonaphthone reached 90 % ee at -30 °C with 2-propanol as the hydrogen source [63]. Even amino acids have been used as ligands for ruthenium [64, but, more than 90 % ee results only when tetralone is the substrate. 

Rhodium-chiraphos cations also hydrogenate ketone and epoxide functionalities, albeit with low optical yields, and are, therefore, not synthetically useful. While this rhodium system seems somewhat limited to the preparation of amino acids, other rhodium and ruthenium catalyst precursors are currently available which show enhanced activity and selectivity for a much broader group of hydrogenation substrates. 

An alternative, new approach for the synthesis of co-carboxamide-containing amino acid derivatives is based on the oxidation of suitably protected a,a-diamino acids (2,4-diamino-butyric acid, ornithine, lysine) with permanganatet or ruthenium(lV) oxide,as shown in Scheme 6. The co-Boc-carboxamide group is stable toward catalytic hydrogenation, acetic acid, and 10% TEA/CH2CI2, is unstable in the presence of 1M NaOH/MeOH, and is cleaved with methanolic hydrazine hydrate, 25% TFA/CH2CI2, 25% HBr/AcOH, or HF.P l... 

Lubell, W. D., Kitamura, M., Noyori, R. Enantioselective synthesis of P-amino acids based on BINAP-ruthenium(ll) catalyzed hydrogenation. Tetrahedron Asymmetry 1991, 2, 543-554. 

Reduction of anilines to cyclohexylamines over RuOj works successfully on a series of nuclear substituted substrates, at 90-125°C, 8 X 10 kPa, in alcohols or without solvent". Yields of 92% are obtained in the preparation of diamines such as bis(4-aminocyclohexyl) methane, the product being mostly cis,cis and cis,trans isomers . Phenylenediamines are reduced to the 1,3-diamine (91%) or to the 1,4-diamine (88%) over ruthenium-on-alumina in ethanol. The c/j-isomer predominates (70-84%) in a number of solvents and over a range of experimental conditions ". Synthetic advantages can be taken from some side reactions. Hydrogenation of 3,4-diaminobenzoic acid can lead to a mixture of bicyclic lactams that lack an amino substituent . Selective hydrogenation of trisubstituted aniline 9 affords lactame 10, an intermediate in the total synthesis of ibogamine. ... 

Homogeneous catalytic asymmetric hydrogenation has become one of the most efficient methods for the synthesis of chiral alcohols, amines, a and (3-amino acids, and many other important chiral intermediates. Specifically, catalytic asymmetric hydrogenation methods developed by Professor Ryoji Noyori are highly selective and efficient processes for the preparation of a wide variety of chiral alcohols and chiral a-amino acids.3 The transformation utilizes molecular hydrogen, BINAP (2,2 -bis(diphenylphosphino)-l,l -binaphthyl) ligand and ruthenium(II) or rhodium(I) transition metal to reduce prochiral ketones 1 or olefins 2 to their corresponding alcohols 3 or alkanes 4, respectively.4... 

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