Hydrogenation derivatives, optical yields

Two kinetic experiments with different CD concentrations were used for kinetic modeling. In this simulation all of the rate constants not involved in the hydrogenation step were not altered. The calculated and simulated kinetic curves and optical yield-conversion dependencies are shown in Figure 9a and 9b. The results of kinetic modeling indicates that the whole kinetic curve and the optical yield - conversion dependencies can be well described by a kinetic model derived from the shielding effect model. 

With DIOP-Pd(0) or -Ni(0) complexes as catalysts, moderate optical yields of up to 35% have been observed (126). Norbomene is convertible to the exo nitrile with up to 40% ee when a BINAP-Pd(0) complex is used (Scheme 57) (127). Ni(0) complexes of sugar-derived 1,2-diol phosphinites catalyze highly selective asymmetric addition of hydrogen cyanide to vinylarenes (128). This method gives the 2-naphthalene-2-propionitrile precursors of nonsteroid anti-inflammatory agents in up to 85% ee and in high yield. 

EDITOR S NOTE In 1982, J Halpem (University of Chicago) reported that rhodium complexes containing chiral phosphine ligands catalyze the hydrogenation of olefinic substrates such as alpha-aminoacrylic acid derivatives, producing chiral products with very high optical yields. 

Knowles next reported optical yields of up to 90% in the hydrogenation of further a-acetamidocinnamic acid derivatives, still using monodentate phosphines chiral at phosphorus. Again the catalysts were prepared in situ from the ligand and [RhCl(l,5-hexadiene)2] or a related complex. The best optical yield of 90% was obtained using cyclohexyl(o-anisyl)methylphosphine (CAMP).224... 

The cyclobutane derivative (55) gave an optical yield of 91% in the hydrogenation of a-acetamidocinnamic acid. The catalyst was here prepared in situ from [RhCl(l,5-hexadiene)]2. The corresponding 1,2-derivative of cyclopentane gave an optical yield of only 73% and the cyclopropane and cyclohexane derivatives gave 15% and 36% respectively.235 [RhCl(cod)2] in presence of the norbomadiene-based ligand NORPHOS (56) gave up to 96% optical yields with a-acetamidocinnamic acid as substrate.236... 

Using a quadridentate ligand derived from 1,3-propanediamine and 2,3-butanedione the cobalt-oxime complex (61) was prepared, and again in presence of the chiral base quinine (60) this was used to hydrogenate benzil according to equation (54) in an optical yield of 79%.277 These cobalt systems permitted only low turnover numbers to be achieved. 

It is difficult to hydrogenate benzoylacetic acid derivatives with a high optical yield. Recently, an (R)-SEGPHOS/Ru complex-catalyzed hydrogenation of the ethyl ester with an S/C of 10,000 under 30 atm of H2 afforded the S alcohol in 97.6% ee (Table of Scheme 20) [36]. MeO-BIPHEP and Tol-P-Phos also performed with a high level of enantioselection [49, 60], Hydrogenation of N-methylbenzoylacetamide with the (R)-BINAP/Ru catalyst gave the S alcohol in >99.9% ee and 50% yield [61]. 

Only limited successful examples of asymmetric hydrogenation of acrylic acids derivatives have included the use of chiral Rh complexes (Scheme 1.17). The diamino phosphine (28) utilizes selective ligation of the amino unit to a Rh center and also exerts electrostatic interaction with a substrate. Its Rh complex catalyzes enantioselective hydrogenation of 2-methylcinnamic acid in 92% optical yield [116], Certain cationic Rh complexes can attain highly enantioselective hydrogenation of trisubstituted acrylic acids [ 1171. 2-(6 -Methoxynaphth-2 -yl)acrylic acid is hydrogenated by an (.S ..S )-BIPNOR- Rh complex in methanol at 4 atm to give (.S)-naproxen with 98% ee but only in 30% yield [26]. 

The chiral titanocene catalyst 34 is very effective for the kinetic resolution of racemic 2,5-disubstituted 1-pyrrolines. When hydrogenation of racemic 5-methyl-2-phenyl-1-pyrroline with (Y)-34 is interrupted at ca. 50% conversion, unreacted R substrate with 99% ee is obtainable with a (2S,5S)-cA-pyrrolidine derivative with 99% ee (Scheme 1.98) [353], As summarized in the table, some other racemic substrates can be resolved in >95% optical yield. 

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

At this point mechanistic studies have reached an impasse. All of the observable intermediates have been characterized in solution, and enamide complexes derived from diphos and chiraphos have been defined by X-ray structure analysis. Based on limited NMR and X-ray evidence it appears that the preferred configuration of an enamide complex has the olefin face bonded to rhodium that is opposite to the one to which hydrogen is transferred. There are now four crystal structures of chiral biphosphine rhodium diolefin complexes, and consideration of these leads to a prediction of the direction of hydrogenation. The crux of the argument is that nonbonded interactions between pairs of prochiral phenyl rings and the substrate determine the optical yield and that X-ray structures reveal a systematic relationship between P-phenyl orientation and product configuration. 

Asymmetric hydrogenation of N-acyl-x-aminocinnamic acids. Rh(I) complexes with either 1 or 2 attached to polymers with suitable swelling characteristics are very effective for asymmetric hydrogenation of dehydroamino acids. Optical yields of about 90% are possible. As expected, polymer-bound Rh(I)-l results in (R)-amino acid derivatives, whereas polymer-bound Rh(I)-2 results in (S)-amino acid derivatives. 

Asymmetric hydrogenation. Procbiral u,/ -unsaturated acids and their derivatives can be hydrogenated with high stereoselectivity by rhodium complexes with 1, such as (BPPM)Rh(COD)Cl and (BPPM)Rh(COD)+ClCV, in which COD = 1,5-eyclooctadiene. The stereoselectivity is dependent in part on the hydrogen pressure, ami the effect can be attenuated by addition of triethylamine, which also increases Ihc optical yield. The stereoselectivity is markedly controlled by the stereochemistry of the double bond.1... 

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