A-Acylaminoacrylic acid

Mibefradil (POSICOR) Asymmetric hydrogenation of a-acylaminoacrylic acids with Stinson (1996)... 

At the same time, Knowles team concentrated their efforts on the use of chiral at phosphorus ligands. Four years after the first report, these authors obtained 88% ee in the reduction of a-acylaminoacrylic acids by incorporating cyclohexyl and ortho-anisyl substituents [44] (Scheme 1.11). 

BINAP-ruthenium dicarboxylate complexes are also efficient catalysts for asymmetric hydrogenation of enamides, a,p- and p,y-unsatu rated carboxylic acids, a-amino ketones, and a-acylaminoacrylic acids.1 2 3 4 5... 

TABLE 1. Asymmetric hydrogenations of a-acylaminoacrylic acids and esters % e.e. using ligand cited with Rh(I) unless otherwise indicated... 

Asymmetric Hydrogenation of a-Acylaminoacrylic Acids with the Soluble DIOP Catalyst11... 

Monsanto ACMP Catalyst Reaction Conditions for Asymmetric Hydrogenations of a-Acylaminoacrylic Acids... 

Reduction of Some a-Acylaminoacrylic Acids (Mainly DOPA Precursors) with Rhodium(I)-Tertiary Phosphine Catalysts (20a)... 

The Monsanto Group has recently reported enantiomeric excesses of 95-96% for the hydrogenation of a-acylaminoacrylic acids using a chiral diphosphine [l,2-di-(0-anisyl-phenylphosphino) ethane] as a ligand (49). The chiral phosphine was prepared by oxidative coupling of chiral o-anisylmethylphenylphosphine oxide (50), followed by deoxygenation with trichlorosilane and tri-n-butylamine in acetonitrile. 

A similar process occurred when the double bond bore a carboxylic function. Reduction of a-acylaminoacrylic acids with the catalytic system (— )-(diop)-Rh(I) allowed an asymmetric hydrogenation with optical yields ranging from 70 to 80%192 (Scheme 131). 

Successively a rhodium chiral biphosphine catalyst ([Rh(l,5-COD)bisphosphine] + BF allowed better selectivity in reducing a-acylaminoacrylic acids (95-96% e.e.)193. 

Asymmetric Hydrogenation Catalyst. Since catalytic asymmetric hydrogenation of a-acylaminoacrylic acid derivatives is an important process to afford a-amino acid derivatives, many rhodium complexes possessing optically active phosphine ligands have been developed in last two decades. [Rh (R)-(la) (cod)]Bp4 (2a) is one of the most efficient catalysts for this purpose with respect to activity and enantioselectivity. Besides (2a), several derivatives, which have various substituents on the nitrogen atom of the pyrrolidine ring, will be mentioned below. 

Asymmetric Hydrogenation.—The asymmetric hydrogenation of a-acylamino-acrylates and cinnamates using chiral rhodium(i) diphosphine complexes as catalysts is now established as one of the best methods for obtaining optically pure a-amino-acids (see previous reviews in this series). In the past year, some new chiral diphosphines have been added to the already considerable number of such ligands. A bis(diphenylphosphino)-derivative of pyrrolidine in conjunction with Rh can be used to hydrogenate a-acetamidocinnamates and itaconic acid with chiral inductions of 90%, whereas an Rh -diphos complex derived from natural tartaric acid effects the reduction of some a-acylaminoacrylic acids to natural (5)-a-acylamino-acids with optical yields of between 80 and 100%. ... 

Unsaturated azlactones and a-acylaminoacrylic acids are converted into o-keto acids by strong mineral acids or alkalies. 

By Chain Lengthening of P-Halo-a-acylaminoacrylic Acid Derivatives. .. 275... 

The reaction of a-keto acids with nitriles in the presence of acid catalysts has also been frequently applied to the preparation of acylaminoacrylic acid derivatives 150, 318, 369). a-Acylaminoacrylic acids are obtained directly from a-halonitriles and excess keto acid under rigorous exclusion of moisture. If the reaction is conducted in the presence of water and excess nitrile, a,a-bis-acetylamino carboxylic acids are formed in very good yields, and can be converted into the acylaminoacrylic acids in a subsequent step. The summary by Greenstein and Winitz 150) should be consulted for more detailed information. 

Olsen et al. (330) describe the reaction of Z-P-halo-a-acylaminoacrylic acid derivatives with lithium dialkyl copper reagents. Replacement of the vinyl halogen by alkyl takes place with complete or predominant retention of configuration at the double bond. 

Hanaki, K., K. Kashiwabara, and J. Fujita Asymmetric Hydrogenation of a-Acylaminoacrylic Acids by the Rhodium (I) Complex of (lR,2i )-Bis(N-diphenyl-phosphinomethylamino)-cyclohexane. Chemistry Letters 1978, 489. 

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