A-Acetamidocinnamic acid

The influence of the concentration of hydrogen in [BMIM][PFg] and [BMIM][BF4] on the asymmetric hydrogenation of a-acetamidocinnamic acid catalyzed by rhodium complexes bearing a chiral ligand has been investigated. FFydrogen was found to be four times more soluble in the [BFJ -based salt than in the [PFg] -based one. 

The cationic [Ir(cod)(bnda)](BF4) complex (bnda = 2,2 -diamno-l,l -binaphthyl), (336), catalyzes the enantioselective hydrogenation of (Z)-a-acetamidocinnamic acid to acetamidodihydrocinnamic... 

A new class of phosphines (30) containing only an axial element of chirality (atropisomerism) has been made (253, 254). An in situ 1 1 rhodium/2,2-bis(diphenylphosphinomethyl)-1,1 -binaphthyl system (30a) hydrogenated a-acetamidocinnamic acid to a 54% ee (S) using 50 atm H2, the solvent not being recorded (253). The corresponding diphenyl-phosphinite system (30b) in toluene-acetone was particularly effective (76% ee) for hydrogenation (95 atm) of a-acetamidocinnamic and a-acet-amidoacrylic esters (254). 

In 1982, Yamashita reported the application of L-talopyranoside-based phos-phine-phosphinite ligand 165 (Fig. 27.15), and found that it induced low enan-tioselectivity (4.7-13% ee) in the hydrogenation of a-acetamidocinnamic acid [119]. Reetz introduced the phosphine-phosphonite ligand (151-153), which led to moderate enantioselectivity (52-88% ee) in the Rh-catalyzed hydrogenation of dimethyl itaconate [120]. The binaphthyl unit remained an essential element in the system. 

Fig. 41.4 Rhodium-catalyzed enantiomeric hydrogenation of a-acetamidocinnamic acid in the system [BMIM][SbF6]/iso-propanol system.

Details of the first stereoselective hydrogenation in ionic liquids were published by the group of Chauvin [68], who reported the enantioselective hydrogenation of the enamide a-acetamidocinnamic acid in the biphasic system [BMIM][SbF6]/ iPrOH (ratio 3 8) catalyzed by [Rh(cod) (-)-diop ][PF6]. The reaction afforded (S)-N-acetylphenylalanine in 64% enantiomeric excess (ee) (Fig. 41.4). The product was easily and quantitatively separated and the ionic hquid could be recovered, while the loss of rhodium was less than 0.02%. 

The same authors compared catalysts prepared from these precursors and [Ru(BINAP)Cl2]2 adsorbed on MCM-41 (with 26 and 37 A pores) and an amorphous mesoporous silica (with 68 A pores) all treated with combinations of SiPh2Cl2 and Si(CH2)3X (X = NH2, CO2H). Catalysts were also prepared in which the organometallic precursors were immobilized by entrapment into silica (using sol-gel techniques). This is one of the few studies in which the performance of chiral phosphine catalysts immobilized by covalent and noncovalent procedures are compared directly. The materials were examined as catalysts for the hydrogenation of sodium a-acetamidocinnamate and of a-acetamidocinnamic acid under similar conditions to those used for the catalysts on unmodified MCM-41. The catalysts... 

With a rhodium complex catalyst containing a chiral ligand dispersed in [BMIM]SbFg, the enantioselective hydrogenation of a-acetamidocinnamic acid to (5)-phenylalanine was achieved with 64% enantiomeric excess 112). [RuCl2( S)-BINAP]2 NEt3 in [BMIM]BF4 for (5)-naproxen synthesis gave 80% ee from 2-(6-methoxy-2-naphthyl) acrylic acid and isopropyl alcohol 214). 

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... 

Ph2P CAPP= pph2 N CONHR R = aryl, alkyl [ RhCl (1,5-hexadiene) ]2 + L Ph2P L= V jW-pph2 N X a-Acetamidocinnamic acid 91 247... 

N-Acetamidoacrylic acid, N-benzoylaminocinnamic acid, 4-acetoxy-3-methoxy-a-acetamidocinnamic acid... 

Place 10.3 g (0.05 mol) of a-acetamidocinnamic acid (Expt 8.21) and 200 ml of 1 m hydrochloric acid in a 500-ml round-bottomed flask and boil the mixture steadily under reflux for 3 hours. Remove a small quantity of green oil by rapidly filtering the hot reaction mixture through a small plug of cotton wool loosely inserted into the stem of a preheated glass filter funnel, cool the filtrate to room temperature and leave it at 0 °C for 48 hours. Collect the crystalline product by filtration, wash it with a small quantity of ice-cold water and dry it in a vacuum desiccator over anhydrous calcium chloride and potassium hydroxide pellets. The yield of phenylpyruvic acid, which is sufficiently pure for most purposes, is 4.4 g, m.p. 157 °C (decomp.). A further 1.7 g of product of comparable purity (total yield 74%) separates from the aqueous acidic filtrate when this is set aside at 0 °C for about one week. 

The insolubilized DIOP catalyst (34) was found to be rather ineffective for the asymmetric hydrogenation of oleflnic substrates the hydrogenation of a-ethyl-styrene proceeded readily but gave (-)-R-2-phenylbutane with an optical purity of only 1.5%. Methyl atropate was hydrogenated to (+)-S-methylhydratropate (2.5% ee). The soluble DIOP catalyst gave 15 and 17% ee, respectively, for the same reductions. The optical purity of the products was lower when recovered insolubilized catalyst was used. There was no reduction of a-acetamidocinnamic acid in ethanol-benzene with the insolubilized catalyst, presumably due to the hydrophobic nature of the polymer support causing it to shrink in hydroxylic solvents. 

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