Acylamino acrylic acids

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

In recent years, the catalytic asymmetric hydrogenation of a-acylamino acrylic or cinnamic acid derivatives has been widely investigated as a method for preparing chiral a-amino acids, and considerable efforts have been devoted for developing new chiral ligands and complexes to this end. In this context, simple chiral phosphinous amides as well as chiral bis(aminophosphanes) have found notorious applications as ligands in Rh(I) complexes, which have been used in the asymmetric hydrogenation of a-acylamino acrylic acid derivatives (Scheme 43). 

Table 2 Enantioselective hydrogenation of a-acylamino acrylic acid derivatives...

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

Compared with 3-alkyl-3-(acylamino)acrylic acid derivatives, much less success has been obtained in the asymmetric hydrogenation of 3-aryl-3-(acylamino)acrylic acid derivatives. An Et-FerroTANE-Rh catalyst has provided up to 99% ee for the hydrogenation of a series of (E)-3-aryl-3-(acylamino)acrylates.95 Since (E)-3-aryl-3-(acylamino)-acrylic acid derivatives are difficult to obtain in large scales compared to (Z)-3-aryl-3-(acylamino)acrylic acid... 

A breakthrough in this area came when Dang and Kagan3 synthesized DIOP, a C2 chiral diphosphine obtained from tartaric acid (Fig. 6-1). DIOP-Rh(I) complex catalyzed the enantioselective hydrogenation of a-(acylamino)acrylic acids and esters to produce the corresponding amino acid derivatives with up to 80% ee. These achievements stimulated research on a variety of bidentate chiral diphosphines, and numerous chiral ligands bearing C2 symmetry have been developed as a result (see Fig. 6-1 for examples). 

Table 12.4 Rh-Catalyzed asymmetric hydrogenation of a-(acylamino)acrylic acids and esters.

Asymmetric hydrogenationRh(I) complcxed with (R)- or (S)-l catalyzes the asymmetric hydrogenation of prochiral a-(acylamino)acrylic acids, R CHC—C-(COOH)NHCOR2, to optically active derivatives of (R)- or (S)-alanine (85 100% ee). 

Current Work and Industrial Applications. Recent efforts have been directed primarily toward refining the original process by using standard o -(acylamino)acrylic acids as substrates. The synthetic efficiency (in-... 

SCHEME 10. Empirical rule in diphosphine-Rh-catalyzed hydrogenation of (Z)-oi-(acylamino)acrylic acids (Ar = aromatic group). 

The reaction of a-oxo acids with nitriles in the presence of an add catalyst gives acylamino acrylic acid derivatives, which are then used to prepare a.P-didehydropeptidesJ85 861 The reaction proceeds with a high degree of purity and is less time consuming. The reaction takes place initially to give the imino chloride 26, which subsequently reacts with the enolic form of the oxo acid. Several a-haloacyl-DHAs 27 have been prepared (Scheme 9) from which the corresponding a-aminoacyl-DHA can be prepared by ammonolysis in aqueous ammonia. 

In the presence of water and excess nitrile a,a-bis(acetylamino) carboxylic acids are formed in very good yields, which can be converted into acylamino acrylic acids in a subsequent step. 

The enantioselective hydrogenation of oc-(acylamino)acrylic acids (Figure 17.77) or a-(acylamino)acrylic acid esters, usually catalyzed by rhodium complexes, is mainly used for... 

Fig. 17.77. Enantioselective homogeneous catalytic hydrogenations of two stereoiso-meric -(acylamino)acrylic acids to one and the same R-amino acid. - The mechanism of the hydrogenation of these acids is exemplified by their Z-isomer Figure 17.78.

Enantioselective homogeneous catalytic hydrogenations of an a-(acylamino)acrylic acid to an R-amino acid. 

Cationic ruthenium bisphosphine complexes, particularly those of BINAP, have been extensively used for the hydrogenation of carbon-carbon double bonds in enamides ". For example, the Ru-BINAP catalyst [Ru(MeOH)2BINAP]BF4 (6.13) is used for the enantiose-lective synthesis of N-acylamino acid 6.15 from a-(acylamino)acrylic acid 6.14. 

Reduction of the enamide double bond of a-(acylamino)acrylic acid 6.16 with Rh complex of diphosphine ligand DIPAMP (5.2) is an important step in the synthesis of L-DOPA (6.17), used for the treatment of Parkinson s disease. 

Enantioselective hydrogenation of certain a- and 3-(acylamino)acrylic acids or esters in alcohols under 1-4 atm H2 affords the protected a- and 3-amino acids, respectively (eqs eq 3 and eq 4). Reaction of N-acylated 1-alkylidene-1,2,3,4-tetrahydroisoquinolines provides the IR- or 15-alkylated products. This method allows a general asymmetric synthesis of isoquinoline alkaloids (eq 5). ... 

Prochiral a-(acylamino)acrylic acids or esters are hydrogenated under an initial hydrogen pressure of 3-4 atm to give the protected amino acids in up to 100% ee (eq 16). The BINAP-Rh catalyst was used for highly diastereoselective hydrogenation of a chiral homoallylic alcohol to give a fragment of the ionophore... 

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