Methyl-2-acetamidoacrylate

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. 

Diels-Alder reaction of methyl 2-acetamidoacrylate with cyclopentadiene in the presence of Si02-Al and Si02-Tl catalysts [53], Rate enhancement was not expressed quantitatively. Reaction conditions a stirred multi-mode tank microreactor, no solvent. 

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. 

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. 

When the peptide synthesis was complete, the phosphines were deprotected by sequential treatment with MeOTf and HMPT (Scheme 36.9). Addition of the rhodium precursor then created the catalyst library, which was screened, on the pin in the enantioselective hydrogenation of methyl-2-acetamidoacrylate (see Scheme 36.10). Unfortunately, this beautiful concept was poorly rewarded with rather low enantioselectivities. 

Table 42.2 Enantioselective hydrogenation of methyl-2-acetamidoacrylate with [RhL COD ]+ SHB catalyst at 298 K in ethanol.

As enantioselective hydrogenations of prochiral substrates are undoubtedly the most common applications of chiral diphosphine ligands, a broad screening of our ligands was undertaken with some commonly used standard substrates. As substrates for the hydrogenation of C=C double bonds dimethyl itaconate (DlMl), methyl 2-acetamidoacrylate (MAA), methyl acetamidocinnamate (MAC) as an a-amino acid precursor, and ethyl (Z)-3-acetamidobutenoate ( 3-ENAM1DE) as a p-amino acid precursor were chosen (see Eig. 1.4.5). 

Figure 8.12 U rea functionalized phosphate ligands for asymmetric hydrogenation of dimethyl itaconate (DMI), N-(3,4-dihydronaphthalen-2-yl)acetamide (DNA) and methyl 2-acetamidoacrylate (MAA).

The A-acylimine-enamide tautomerism of methyl 2-acetamidoacrylate has been studied641 by means of ab initio calculations. A 13C NMR investigation has been undertaken to study the tautomerism between the hydrazone imine and diazenylen-amine forms of 3-(arylhydrazono)methyl-2-oxo-l,2-dihydroquinoxalines,642 and the effects of temperature and side-chain on the imine-enamine tautomerism in quinoxalinone and pyridopyrazinone systems have been studied.643 A detailed... 

C6H9N03 methyl 2-acetamidoacrylate 35356-70-8 25.00 1.1467 2 7826 C6H10O2 4-methyl-2-pentenoic acid 10321-71-8 21.00 0.9529 1... 

In water the hydrogenation rate and the enantioselectivities were considerably lower. However, the addition of amphiphiles as proposed by G. Oehme mediates the dispersion of the relatively hydrophobic reactants and effects an enormous increase in hydrogenation activity and selectivity [17, 24, 25]. Fig. 10 depicts the results of the model hydrogenation reaction of methyl 2-acetamidoacrylate lc (see... 

Table 6.11 Catalyst screening for the asymmetric hydrogenation of methyl-2-acetamidoacrylate (127).

More recently, de Bellefon and co-workers [74] demonstrated the asymmetric hydrogenation of methyl-2-acetamidoacrylate (127) to 128, within a glass capillary reactor (530 pm i.d.). Employing MeOH as the reaction solvent, H2 (1-5 bar), and a residence time of 1 min, the chiral phosphines (R,R)-DIOP (129), (R)-PHANPHOS (130), and (R,S)-Cy,Cy-J OSIPHOS (131) were evaluated as chiral promoters in the model reaction (Table 6.11). Using this approach, the authors were able to screen the catalysts using only 100 pi of reaction mixture, readily identifying 130 as the most suitable catalyst for the transformation. 

Thermal decomposition of l,4-dihydro-2,3-benzoxathiin 3-oxides generates o-xylylenes which can be trapped by methyl 2-acetamidoacrylate yielding tetralin-based a-amino acids <04S558>. A phosphazene base [EtN=P(NMe2)2(N=P(NMe)2)3)] is used to generate the ylide from chiral oxathiane 74 in a two-step asymmetric synthesis of aziridines from tosylimines <04JOC1409>. 

Four substrates were chosen for our study, methyl-2-acetamidoacrylate 2, methyl acetamidociimamate 3, dimethyl itaconate 4 and the Candoxatril precursor 5 (6) (Figure 1). The precatalysts [(/ ,/ )-Me-DuPHOS Rh (NBD)]BF4, (R.R)-7n, and [(5,5)-Et-DuPHOS Rh (NBD)]BF4, (.S, 5)-7b, were prepared according to literature... 

Hydrogenation of methyl-2-acetamidoacrylate 2 with (R,R)-7z, at 1000/1 molar substrate/catalyst (S/C) ratio was very fast and reactions were complete in less than 10 minutes giving (/ )-methyl //-acetyl alanine in > 99 % e.e. (3 bar H2 pressure, room temperature). Under the same conditions, (S,S)-6a, gave (5)-methyl Macetyl alanine in > 99 % e.e. Conpetition reactions were carried out in order to gain a measure of the relative productivity of the two catalysts. These experiments involved using an equimolar mixture of (5,5)-6a and (R,R)-7a in the same reaction. Since the precatalysts have opposite enantiomers of ligand, then the closer the overall productivity given by the NBD and COD precatalysts, the... 

Scheme 8.34 Rhodium-catalyzed enantioselective arylation of methyl-2-acetamidoacrylate (133).

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