Esters a-dehydroamino acid

Table 2 Asymmetric hydrogenation of / ,/3-dimethyl a-dehydroamino acid esters...

The hydrogenation of />,/>-disubsti tilled a-dehydroamino acids remains a relatively challenging problem. The Rh complexes of chiral ligands such as Cy-BisP [58a], MiniPhos [65], and unsymmetrical BisP 13 [67b] have shown high efficiencies for some / ,/ -disubstituted a-dehydroamino acid substrates. Some efficient examples of hydrogenation of / ,/1-dimethyl a-dehydroamino acid esters with different chiral phosphorus ligands are listed in Table 26.2. 

Shin, C., K. Nanjo, E. Ando, and J. Yoshimura a,p-Unsaturated Carboxylic Acid Derivatives. VI. New Synthesis of N-Acyl-a-dehydroamino Acid Esters. Bull. Chem. Soc. Japan 47, 3109 (1974). 

Figure 4.22 Modular chiral dendritic chiral monodentate phosphoramidite ligands for the Rh-catalyzed asymmetric hydrogenation of a-dehydroamino acid esters.

With 56g as the heterogeneous catalyst, asymmetric hydrogenation of a-dehydroamino acid esters 48b and 48c, enamide 50a, and itaconic acid ester 57 were performed in toluene at room temperature under 40 atm of H2 to afford the corresponding products with full conversion in 90-97% ee, which were comparable or even superior to those obtained with their homogeneous counterpart (MonoPhos)2/Rh(I). Upon completion of the reaction, the catalyst... 

Several accounts have described (Z)-dehydroamino acid esters as being less active than the corresponding (F)-isomer [59c, 143-145]. In fact, Bruneau and Demonchaux reported that when reduction of an (E/Z)-mixture of 73 with Rh-Et-DuPhos in THF was not complete, only unreacted (Z)-73 was detected. These findings conflict, however, with results obtained in MeOH [56 d], where the ligand structure was also found to be significant to the relative reactivity of each stereoisomer. As for a-dehydroamino acid derivatives, preformed metal-diphosphine complexes generally perform in superior fashion to those prepared in situ [56d]. 

Several phospholane-based ligands have shown a wide substrate scope beyond the standard examples represented in Table 24.2. Both Et-FerroTANE 61 [147] and TangPhos 46 [69 b, 71] have been successfully applied to a diverse range of methyl and ethyl />-aryl-dehydroamino acids containing various aromatic substituents, whilst catASium M 20a [95] has been used for the reduction of numerous yS-alkyl-dehydroamino acid esters. 

Many synthetic applications of Rh-catalyzed hydrogenation of a-dehydroamino acid derivatives have recently been explored (Scheme 26.2). Takahashi has reported a one-pot sequential enantioseiective hydrogenation utilizing a BINAP-Rh and a BINAP-Ru catalyst to synthesize 4-amino-3-hydroxy-5-phenylpentanoic acids in over 95% ee. The process involves a first step in which the dehydroami-no acid unit is hydrogenated with the BINAP-Rh catalyst, followed by hydrogenation of the / -keto ester unit with the BINAP-Ru catalyst [87]. A hindered pyridine substituted a-dehydroamino acid derivative has been hydrogenated by a... 

Several chiral phosphorous ligands with great structural diversity are effective for the rhodium-catalyzed hydrogenation of a-dehydroamino acid derivatives. Tab. 1.1 summarizes the asymmetric hydrogenation of (Z)-2-(acetamido)ciimamic acid, 2-(acetamido)acrylic acid, and their methyl ester derivatives. 

Dipolar Cycloaddition Reactions. Dehydroamino acid derivatives behave as dipolarophiles in 1,3-dipolar cycloaddition reactions that leads to a variety of interesting compounds. For example, 1,3-dipolar cycloaddition of diazomethane to dehydroamino acid esters 475 and 481 gives the corresponding pyrazolines 476 and... 

Table 2.4 Asymmetric hydrogenation of dehydroamino acid esters and a-enamides catalyzed hy Rh(I)-f-Bu-QuinoxP (see Figure 2.3)...

OL, -Dehydroamino acids. N-Protected (Cbo and Boc) (3-hydroxy-a-amino acid esters (ethyl, benzyl) are converted into the corresponding a,p-dehydroamino acid derivatives by DAST and pyridine in CHiCl, at 0° (6.5-90% yield). The hydroxy group is probably converted into the —OSFiNlCiH,), derbative, which undergoes trans-e m -... 

Schmidt, U., Lieberknecht. A.. Schanbacher. U.. Beuttler. T.. and Wild, J., Facile preparation of N-acyl-2-(diethoxyphosphoryl)glycine esters and then- use in the synthesis of dehydroamino acid esters, Angew. Chem. Int. Ed. Engl.. 21. 776. 1982. 

The most commonly employed substrates are (Z)-a-acetamidocinnamic acid (ACA), its methyl ester (MAC), acetamidoacrylic acid (AAA) and its methyl ester (MAA). Quantitative yields at mild hydrogen pressure (1-3 atm) are usually obtained with these substrates. Values of ee very close to 100% have been reached for dozens ligands, including many P-stereogenic phosphines. The most successful examples of the hydrogenation of a-dehydroamino acid derivatives are listed in Table 7.1. 

Typical examples of this elass of substrates include atropic acid (AA), ita-conic acid (lA) and their methyl esters. With those substrates enantioselec-tivities tend to be somewhat lower eompared to a-dehydroamino acids/ but at present many P-stereogenie ligands have provided excellent results (Table 7.4). 

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