A,P-unsaturated carboxylic acid derivatives

Table 2.1.5.3 Asymmetric hydrogenation of a, P-unsaturated carboxylic acid derivatives.

The asymmetric aziridination of a, P-unsaturated carboxylic acid derivatives is a direct route to optically active aza-cyclic a-amino acids, and this class of chiral aziridines can also be used as chiral building blocks for the preparation of other amino acids, P-lactams, and alkaloids. Prabhakar and coworkers carried out an asymmetric aziridination reaction of tert-butyl acrylate with O-pivaloyl-N-arylhydroxylamine 25 in the presence of cinchonine-derived chiral ammonium salt 2e under phase-transfer conditions, which furnished the corresponding chiral N-arylaziridine 26 with moderate enantioselectivity (Scheme 2.24) [46],... 

Sdieme 3.39. Reactions between a-aminoall lcuprates and a,p-unsaturated carboxylic acid derivatives [161]. 

Nagata, W., Yoshioka, M. Hydrocyanation and its application to steroid syntheses. Proc. Int. Congr. Horm. Steroids, 2nd 1967, 327-335. Nagata, W., Okumura, T., Yoshioka, M. Hydrocyanation. VIII. Conjugate hydrocyanation of steroidal a,P-unsaturated carboxylic acid derivatives. J, Chem. Soc. C. 1970, 2347-2355. 

Alkylations ofDienolates of a,P-Unsaturated Carboxylic Acid Derivatives... 

Shin, C.G., Yonezawa, Y, Sekine, Y, and Yoshimura, J., a,P-Unsaturated carboxylic acid derivatives. Part 7. Reaction of ethyl a,P-unsaturated a-cyanocarboxylates with triethyl or diethyl phosphonate, Bull. Chem. Soc. Jpn., 48, 1321, 1975. 

Tandem reactions have emerged as promising procedures for the synthesis of highly functionalised compounds in a single step. Horner-Wadsworth-Emmons reactions have been coupled with 1,4-Michael additions to prepare 6-substituted a,p-unsaturated carboxylic acids derivatives, and with Diels-Alder reactions, which utilised sugar-derived phosphonate (176) to prepare enantiomerically pure bicyclo[4.3.0]nonanes. ... 

Thermal and Lewis acid-catalyzed reactions of 1-thia-l,3-dienes with chiral a,P-unsaturated carboxylic acid derivatives lead to thiopyrans. The cycloadditions of chiral a,p-unsaturated oxazolidinones in the presence of aluminum Lewis acids lead to encouraging stereoselectivities. Cleavage of the chiral auxiliaries was achieved by treatment with LiAlHi. 

The addition of nitrile oxides to a,P-unsaturated carboxylic acid derivatives opens up a route to chiral, substituted isoxazoline derivatives. The nitrile oxides are generated in situ via deprotonation with a base (e.g. triethylamine) starting from the chlorinated aldoxime as the precursor (solvents CHCI3, CH2CI2, ether, benzene, toluene temperature -78°C up to 110°C). In most cases only one of two possible regioisomeric adducts is formed. 

Aziridines of type A, with a chiral substituent located at the nitrogen atom have been applied successfully in asymmetric syntheses with a,p-unsaturated carboxylic acid derivatives derived from Oppolzer s chiral camphor sultam. " ... 

Four-Component Synthesis of Pyrrolopyridines If a primary amine were used as an input, the three-component reaction shown in Scheme 15.10 would produce an oxazole bearing a secondary amine. In other words, the so-produced adduct 24 would contain both a diene (oxazole) and a nucleophilic site (amine). Therefore, a dienophile bearing an electrophihc center would pair perfectly with the dual reactivity of 24. In practice, if an activated a,P-unsaturated carboxylic acid derivative were introduced after the three-component reaction, a sequence of N-acylation/intramolecular Diels-Alder reaction (IMDA) might occur to produce the four-component adducts. 

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). 

The conjugate addition of cyanide to a,p-unsaturated carboxylic acid derivatives provides versatile chiral building blocks. The resulting -cyano adducts can be converted into y-aminobutyric acids (GABA analogues) under reducing conditions, 1,2-dicarboxylic acids via hydrolysis, and -amino acids via Curtius rearrangement. 

A silver-ion assisted halohydrin formation from a,p-unsaturated carboxylic acid derivatives was performed with chiral A-enoyl-2-oxazolidinones to form awri-o -halo- S-hydroxy carbonyls in good yields (90-94%, eq 2S). This alternate method of carboxyhalohydrin asymmetric-synthesis produced better diastereoselectivity (up to S,S RJi = 80 20) with AgOAc (or AgNOg) than with Ag2C03. The observed stereoselectivity required a nonnucleophilic (alkyl) substituent on the oxazolidi-none chiral auxiliary. 

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