2-Acetamidoacrylate, hydrogenation

Another important example of an enantioselective reaction mediated by a chiral catalyst is the hydrogenation of 3-substituted 2-acetamidoacrylic acid derivatives. 

Scheme 8.3 Hydrogenations of substituted acetamidoacrylates with thioether-phos-phinite ligands.

On the other hand, Bolm et al. have reported, more recently, the use of BINOL-derived A -phosphino sulfoximines as ligands in the rhodium-catalysed hydrogenation of dimethyl itaconate and a-acetamidoacrylates, achieving excellent enantioselectivities of up to 99% ee (Scheme 8.12). In the main... 

Scheme 8.22 Hydrogenation of acetamidoacrylic acid with iridium complexes containing dithioether ligands.

Fig. 5.1. Mechanism of ruthenium catalyzed enantioselective hydrogenation of a-acetamidoacrylate esters. Reproduced from J. Am. Chem. Soc124, 6649 (2002), by permission of the American Chemical Society.

Complex 7-AI2O3/PTA/ (/< ./< )-(Mc-DuPHOS)Rh(COD) 1 (1) was prepared and tested in the hydrogenation of the prochiral substrate methyl-2-acetamidoacrylate (MAA). After full conversion, the products were separated from the catalyst and analyzed for Rh and W content and product selectivity. The catalyst was re-used three times. Analytical results show no rhodium leaching is observed. Complex 1 maintains its activity and selectivity in each successive run. The first three runs show tungsten (W) leaching but after that no more W is detectable. The leached W comes from the excess of PTA on alumina. The selectivity of both tethered and non-tethered forms gave the product in 94% ee. 

The rhodium complexes with hydroxyphospholane ligand 125663 or 126660 catalyze the asymmetric hydrogenation of a-acetamidoacrylates with ee values in excess of 98%. System 125 is also very effective in the asymmetric hydrogenation of P-acetamidoacrylates (up to 99.6% ee).664 The planar-chiral heterocyclic ligand 127 complexed with rhodium(I) catalyzes the hydrogenation of a-acetamidoacrylates in excellent yields and ee values from 79-96% under mild conditions.665... 

Other systems that prove successful in the highly enantioselective hydrogenation of a-acetamidoacrylates include the spirophosphinites 128 (94.2-97.2% ee)666 and the Josiphos ligands 129 with rhodium(I) (84-96% ee). Excellent... 

Enamides, in addition to the acrylates shown above, are also asymmetrically hydrogenated with many of the same systems that prove useful for the acetamidoacrylate reductions. The Rh(I)/BICP (2(/J)-2/(i)-bis(dipenylphosphino)-1(R),] (R)-dicyclopenlane) 132 and Rh(I)/DuPHOS systems work well (>90% ee) for the asymmetric hydrogenation of /3-acctamidovinyl methoxymethyl ethers... 

Using unmodified Ru-BINAP and Rh-Et-DUPHOS catalysts Jacobs et al. performed hydrogenation reactions of dimethylitaconate (DMI) and methyl-2-acetamidoacrylate (MAA), respectively. [11,47] The continuous hydrogenation reaction was performed in a 100 mL stirred autoclave containing an MPF-60 membrane at the bottom, which also acts as a dead-end membrane reactor. The hydrogenation reactions will be discussed in paragraph 4.6.1. 

The bis-DIOP complex HRh[(+)-DIOP]2 has been used under mild conditions for catalytic asymmetric hydrogenation of several prochiral olefinic carboxylic acids (273-275). Optical yields for reduction of N-acetamidoacrylic acid (56% ee) and atropic acid (37% ee) are much lower than those obtained using the mono-DIOP catalysts (10, II, 225). The rates in the bis-DIOP systems, however, are much slower, and the hydrogenations are complicated by slow formation of the cationic complex Rh(DIOP)2+ (271, 273, 274) through reaction of the starting hydride with protons from the substrate under H2 the cationic dihydride is maintained [cf. Eq. (25)] ... 

Zhang reported two new (S)-BINOL based ligands phosphine-phosphite (S,R)-o-BINAPHOS 163 and phosphine-phosphinite (S)-o-BIPNITE 164 [128]. Applications of these ligands in the Rh-catalyzed hydrogenation of methyl N-2-acetamido-cinnamate and methyl N-2-acetamidoacrylate induced very high enantioselectiv-ities (>99% ee), and with a wide range of substrates. 

Salzer et al. prepared a set of planar-chiral diphosphine ligands based on the arene chromium tricarbonyl backbone (Fig. 36.3) [21]. The straightforward four-step synthetic route allowed the preparation of 20 ligands of this family. These ligands were tested in Ru- and Rh-catalyzed enantioselective hydrogenation of various substrates, including the standard C=C substrates (dimethyl itaconate, methyl-2-acetamidocinnamate, methyl-2-acetamidoacrylate) as well as MEA-imine (l-(methoxymethyl)ethylidene-methylethylaniline) and ethyl pyruvate. Moderate conversions and ee-values were obtained. 

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