A-amino acids ester

Aluminum chloride [7446-70-0] is a useful catalyst in the reaction of aromatic amines with ethyleneknine (76). SoHd catalysts promote the reaction of ethyleneknine with ammonia in the gas phase to give ethylenediamine (77). Not only ammonia and amines, but also hydrazine [302-01-2] (78), hydrazoic acid [7782-79-8] (79—82), alkyl azidoformates (83), and acid amides, eg, sulfonamides (84) or 2,4-dioxopyrimidines (85), have been used as ring-opening reagents for ethyleneknine with nitrogen being the nucleophilic center (1). The 2-oxopiperazine skeleton has been synthesized from a-amino acid esters and ethyleneknine (86—89). 

Formation of Diketopiperazines. Esters of a-amino acids can be readily prepared by refluxing anhydrous alcoholic suspensions of a-amino acids saturated with dry HQ. Diketopiperazines are formed by heating the alcohohc solution of the a-amino acid ester. 

An unusual approach to the lumazine nucleus was found in the photochemical transformation of 6-azido-l,3-dimethyluracil (289) with various amino compounds (78JA7661). Irradiation of (289) in the presence of ethyl a-amino acid esters forms 7-substituted 7,8-dihydrolumazin-6-ones (288), and with a-aminoketones 6-substituted 7,8-dihydro-lumazines (290) are formed (equation 103). 

An approach to the preparation of asymmetrically 1,2-disubstituted 1,2-diamines has been reported the zinc-copper-promoted reductive coupling of two different N-(4-substituted)phenyl aromatic imines, one bearing a 4-methoxy and the other a 4-chloro substituent, in the presence of either boron trifluoride or methyltrichlorosilane, gave a mixture of the three possible 1,2-diamines, where the mixed one predominated [31 ]. Low degrees of asymmetric induction were observed using 1-phenylethylamine, phenylglycinol and its 0-methyl ether, and several a-amino acid esters as the chiral auxiharies meanwhile the homocoupling process was not avoided (M.Shimizu, personal communication). 

The chloro bridges in rir(cod)Cll2 are cleaved by a-amino acid esters to yield r(cod)Ir(Cl)(L)l (L = GlyOEt, L-AlaOMe, L-ValOMe).694... 

Synthetic work commenced with evaluation of an azomethine ylide dipole for the proposed intramolecular dipolar cycloaddition. A number of methods exist for the preparation of azomethine ylides, including, inter alia, transformations based on fluoride-mediated desilylation of a-silyliminium species, electrocyclic ring opening of aziridines, and tautomerization of a-amino acid ester imines [37]. In particular, the fluoride-mediated desilylation of a-silyliminium species, first reported by Vedejs in 1979 [38], is among the most widely used methods for the generation of non-stabilized azomethine ylides (Scheme 1.6). 

Bis-a-amino acid esters 35 were prepared by use of the N-anthracenylmethyl catalysts 12 (R=H, X=C1) or its dihydro derivative 12 (R=H, X=Br, 10,11-dihydro) with high diastereo and enantioselectiv-ities via alkylation of two equivalents of the O Donnell imine 23 with appropriate dibromides 33, as summarized in Table 3.130311... 

O Donnell imine 23 with various aldehydes, giving P-hydroxy-a-amino acid esters 44 with high enantiomeric excess,1401 as shown in Scheme 15. 

M. Horikawa, J. Bush-Petersen, E. J. Corey, Enantioselective Synthesis of P-Hydroxy-a-amino Acid Esters by Adol Coupling Using a Chiral Quaternary Ammonium Salt as Catalyst , Tetrahedron Lett. 1999, 40, 3843-3846. 

At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

Racemic a-amino acid esters have been converted to single enantiomers by condensing them with 2-hydroxypinan-3-one (91), and then diastereoselectively protonating the resultant chiral Schiff base. ... 

Diazepines represent an important class of bicyclic seven-membered heterocycles. They are the basis of several tranquilizers and are accessible from a-amino acid esters and o-azidobenzoyl chloride in the presence of triethylamine. The A/ -(o-azidobenzoyl)amino esters (333) formed in this way (Scheme 121) are cyclized by Staudinger and aza-Wittig reactions to give 2-ethoxy-l,4-benzodiazepin-5-ones (334) (92MI2). 

The method was successfully employed with enolizable esters, including chiral a-amino acid esters and peptides, and no trace of racemization/epimerization at the a carbon was detected. 

Fig. 5.6 Oxidation of cyclic a-amino acid esters with RuO [42]...

TABLE 5.2. SYNTHESIS OE 5-AEKOXY-2(3H)-OXAZOEONES EROM a-AMINO ACID ESTERS... 

Dialkoxy-2-oxazolidinones 295, which are prepared by reaction of 5-alkoxy-2(3//)-oxazolones 47 with acetals in the presence of Lewis acid catalysts, are hydrolyzed in the presence of a protonic acid to produce a-amino acid esters 296 (Fig. 5.70 Table 5.11, Fig. 5.71 Table 5.12, Fig. 5.72 Table 5.13, Fig. 5.73 Table 5.14, Fig. 5.74). ... 

TABLE 5.14. SYNTHESIS OE a-AMINO ACID ESTERS EROM 5,5-DIAEKOXY-2-OXAZOEIDINONES"... 

In a similar way, propargyl esters of A -benzoyl-a-amino acids have been converted into a-allenyl-a-amino acid esters 113 by cyclization to oxazoles 111 followed by Claisen rearrangement to the 4-allenyl-2-phenyl-5(4//)-oxazolones 112. Oxazolone ring opening with methanol then afforded 113 (Scheme 7.32). ... 

Finally, it is noted that suitable enantiomers of helicenes have been applied as selector for non-helical compounds. The disodium salt of P-( +)-7,10-dicarboxy hexahelicene coated on silicagel was successfully used in resolving the N-(2,4-dinitro-phenyl)-a-amino acid esters. Good resolutions were found for alanine, isoleucine, valine, phenylalanine and phenylglycine 94). 

Bis-p-nitrophenyl malonate (55M29) reacts with a-alkylamino-isobutyr-onitriles in xylene to give derivatives (16b) of tetramic acids with yields of 30-50% (86UP1 88UP1). The reaction of derivatized malonic acids with a-amino acid esters to 3-alkoxycarbonyl-l,5-dihydro-4-hydroxy-2-pyrrolones presents the same problems (see Section III). (See Fig. 8.)... 

Simple esters cannot be allylated with allyl acetates, but the Schiff base 109 derived from a-amino acid esters such as glycine or alanine is allylated with allyl acetate. In this way. the a-allyl-a-amino acid 110 can be prepared after hydrolysis[34]. The a-allyl-a-aminophosphonate 112 is prepared by allylation of the Schiff base 111 of diethyl aminomethylphosphonates. [35,36]. Asymmetric synthesis in this reaction using the (+)-AV-dicycIohex-ylsulfamoylisobornyl alcohol ester of glycine and DIOP as a chiral ligand achieved 99% ee[72]. 

The reaction of several a-amino acid esters with 0-lactones in chloroform solution gave hydroxyamide esters (equation 50), said to be useful fungicides (74JAP(K)74127918>. Enamines derived from cyclohexanone react smoothly with 0-propiolactone to give 3-(2-cyclo-hexanonyl)propionamides in reasonable yields (equation 51). No acylation of the enamine is observed. This reaction has been used as a key step in a new synthesis of 8-aza steroids (75JOC50). Cyclohexanone imines react in the same manner, except that the expected initial product cyclizes to give bicyclic lactams and enaminones (equation 52) (80T3047). 

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