Asymmetric Hydrogenation with Rhodium Complexes

Achiral Wilkinson s catalyst, RhCljPPhaja, is an effective homogeneous catalyst for the hydrogenation of alkenes. The first examples of homogenous asymmetric hydrogenation were reported independently by Horner and Knowles. These were variants of Wilkinson s catalyst using enantiomerically pure monodentate 

Catalysis in Asymmetric Synthesis 2e 2009 Vittorio Caprio and Jonathan M.J. Williams 

Initial research in this area focussed on the development of enantiomerically pure bidenate bisphosphines, often possessing C2-symmetry, as ligands in the hydrogenation of alkenes, and the a-(acylamino)acrylic acids have remained popular substrates. Many of these ligands have provided high enantioselectivity in the reduction of enamides, and a representative set of such structures (2.04-2.15) is shown, all of which have given over 90% ee (often higher).  

Recent research has shown that this mechanism does not hold for all catalyst and substrate combinations. For instance, the rhodium-catalysed hydrogenation with electron-rich bidentate phosphine (2.11) is thought to proceed via initial oxidative addition of hydrogen to a catalyst-substrate complex. Furthermore, enantioselectivity arises from reaction of the major catalyst-ligand complex, in a lock-and-key process, when using monodentate phosphites as ligands. 

The diene (2.32) undergoes selective hydrogenation of the enamide double bond to give an amino acid derivative (2.33) containing an alkene functionality. The most enantioselective catalyst for this reaction was found to be the cationic rhodium complex of DUPHOS (2.05), which afforded less than 1% of the fully hydrogenated product as a by-product. 

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Morimoto T, Chiba M, Achiwa K. Catalytic asymmetric hydrogenation with rhodium complexes of improved DIOPS bearing para-dimethylamino group on the basis of our designing concept. Tetrahedron Lett. 1988 29(37) 4755 758. 

W. Knowles, M. Sabacky, B. Vineyard, D. Weinkauff, Asymmetric hydrogenation with a complex of rhodium and a chiral bisphos-phine, J. Am. Chem. Soc. 1975, 97, 2567-2568. 

A number of catalysts with the catalytic site in the dendrimer core has also been used in asymmetric hydrogenation. A rhodium complex with dendrimer diphos-phine with menthyl groups in its branches as a catalyst in acetamidocinnamic acid hydrogenation exhibited low enantioselectivity. For a catalyst where dendrimers were at the meta positions of phosphine, the reaction rate was substantially higher than that for a low molecular weight analogue and for a catalyst where dendrimers were at positions 2 and 5 of phosphine, the reaction rate was much lower [134-137],... 

Hayashi, T., M. Tanaka, and I. Ogata Asymmetric Hydrogenation by Rhodium Complex with d-rrfl 5-l,2-bis-(Diphenylphosphinoxy)-cyclopentane as a Chiral Ligand. Tetrahedron I.etters 1977, 295. 

One of the success stories of transition metal catalysis is the rhodium-complex-catalyzed hydrogenation reaction. Asymmetric hydrogenation with a rhodium catalyst has been commercialized for the production of L-Dopa, and in 2001 the inventor, Knowles, together with Noyori and Sharpless, was awarded the Nobel Prize in chemistry. After the initial invention, (enantioselective) hydrogenation has been subject to intensive investigations (27). In general, hydrogenation reactions proceed... 

Asymmetric Hydrogenation. Asymmetric hydrogenation with good enantio-selectivity of unfunctionalized prochiral alkenes is difficult to achieve.144 145 Chiral rhodium complexes, which are excellent catalysts in the hydrogenation of activated multiple bonds (first, in the synthesis of a-amino acids by the reduction of ol-N-acylamino-a-acrylic acids), give products only with low optical yields.144 146-149 The best results ( 60% ee) were achieved in the reduction of a-ethylstyrene by a rhodium catalyst with a diphosphinite ligand.150 Metallocene complexes of titanium,151-155 zirconium,155-157 and lanthanides158 were used in recent studies to reduce the disubstituted C—C double bond with medium enantioselectivity. 

A review of asymmetric hydrogenation of ketones with rhodium complexes as catalysts has been presented.330 A review of the developments in the asymmetric hydrogenation of ketones with ruthenium complexes as homogenous catalysts of hydrogenation, with particular emphasis on the work of Halpern, has been presented.331... 

Yamaguchi H, Hirano T, Kiminami H, Taura D, Harada A. Asymmetric hydrogenation with antibody-achiral rhodium complex. Org. Biomol. Chem. 2006 4 3571-3573. 

Catalytic asymmetric hydroboration has been most extensively studied with styrene (4) as the substrate which produces 1-phenylethanol (6) after treatment of the hydroboration product, l-phenyl-l,3,2-benzodioxaborole (5), with alkaline hydrogen peroxide (Scheme 2). The regioselectivity favoring the branched isomer 5 over the linear isomer 5 is usually high when the reaction is carried out with rhodium complexes coordinated with chelating ligands such as bisphos-... 

Two ruthenium complexes, binap 3.43-Ru(OCOR)2(R = Me,CF3) [892] and binap 3.43-RuX2 (X = Cl, Br, I) [893, 894], are quite useful. The acetate and trifluoroacetate complexes of 3.43 induce selective asymmetric hydrogenations of classes of prochiral olefins that are poorly selective with rhodium complexes. These classes include a,(3- or fcy-unsaturated acids and esters, ally alcohols, j3-acylaminoacrylates and enamide precursors of isoquinoline alkaloids [752, 853, 859, 881, 883, 895]. 

Directed and Asymmetric Reduction The principles of directed and asymmetric reactions were first developed for hydrogenation, as discussed in Section 9.2. Asymmetric hydrosilation of ketones can now be carried out cata-lytically with rhodium complexes of diop (9.22). The new chiral ligand Et-duPHOS, made by Burk at du Pont, allows chiral amination of ketones via Eq. 14.50. Note how the use of the hydrazone generates an amide carbonyl to act as a ligand, as is known to favor high e.e. (see Section 9.2). Noyori s powerful BINAP ligand has been applied to a large number of asymmetric reactions. 

Figure 18.1 Asymmetric hydrogenation with avidin containing a biotinyiated phosphine-rhodium (I) complex [1].

Achl978 Achiwa, K., Catalytic Asymmetric Hydrogenations with Polymer Supported Chiral Pyrrolidinephosphine-Rhodium Complexes, Chem. Lett, (1978) 905-908. 

Morrison JD, Burnett RE, Aguiar AM, Morrow CJ, Phillips C. Asymmetric homogeneous hydrogenation with rhodium (I) complexes of chiral phosphines. J. Am. Chem. Soc. 1971 93(5) 1301-1303. 

Morimoto T, Chiba M, Achiwa K. Efficient synthesis of natural (-f)-collinusin using catalytic asymmetric hydrogenation with a chiral biphosphine-rhodium(I) complex. Chem. Pharm. Bull. 1989 37(12) 3161-3163. 

Achiwa, K. Asymmetric Hydrogenation with New Chiral Functionalized Bis-phosphine-Rhodium Complexes. J. Amer. Chem. Soc. 98, 8265 (1976). 

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

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