Amines 1-Amino acid esters

Table 11. 1 H-NMR Analysis of Amines. Amino Acids, Esters, Peptides and Hydroxylamines via (/ ./ )-0,0 -Dibenzoyltartaric Acid Imides (5, CDC13)50...

Fischer carbenes behave chemically as if a considerable positive charge resides on the carbene carbon atom. They are, for example, susceptible to nucleophilic substitution by a range of reagents such as amines, amino acid esters, thiols, alcohols, alkoxides and carbon nucleophiles. The reactions with amines are assisted by hydrogen bonding to excess reagent or to the solvent. 

The industrial process for preparing the reagent usually permits a little hydrolysis to occur, and the product may contain a little free calcium hydroxide or basic chloride. It cannot therefore be employed for drying acids or acidic liquids. Calcium chloride combines with alcohols, phenols, amines, amino-acids, amides, ketones, and some aldehydes and esters, and thus cannot be used with these classes of compounds. 

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). 

Sodium triacetoxyborohydride is an alternative to NaBH3CN for reductive amination. This reagent can be used with a wide variety of aldehydes or ketones with primary and secondary amines, including aniline derivatives.93 This reagent has been used successfully to alkylate amino acid esters.94... 

Belleau and Malek47 introduced the use of this reagent (EEDQ) to couple acylamino acids with amino acid esters, and Dunstan and Hough46 were able to couple the peracetates of maltosyl-, lactosyl-, and cello-biosyl-amine (55, 47, and 57, respectively) with 1-benzyl N-(benzyl-... 

Spin-labeled phosphoramidates are synthesized analogously by the reaction of phosphoric imidazolides with primary or secondary amines[189] or amino acid esters.11883... 

Possible racemisation of imines, derivatives of amino acids and R(—)-myrtenal, has been examined by Dufrasne et al.1 After 72 h, no significant effect on chiral purity was observed. For imines being derivatives of chiral primary amines and the a-substituted 8-keto-aldehydes, no evidence of epimerisation has been indicated by the NMR measurements.3 For a series of imines, being derivatives of amino acids or amino acid esters and (R)-BINOL reagents, Chin et al.5 have tested the possibility of epimerization under experiment conditions. It was shown that R S ratio has changed only slightly, and after 24 h, the difference was lower than 10%. 

Twenty one rhena-/3-ketoimine derivatives of 14 different amino acids and one dipeptide have also been synthesized (37,38). The amino acid derivatives are prepared according to Eq. (3) in which the primary amine is an amino acid ester. A dipeptide derivative is formed via normal peptide coupling reactions, as shown in Eq. (4). In this reaction sequence, the ethyl... 

O-H stretch 3300-2500 broad Amines, primary -NH2 Amino acids Esters N-H stretch 3500-3400 doublet, weak NH3 stretch 3100-2600 strong C=0 stretch 1750-1735... 

R Schwyzer, M. Feuer, B Iselin. Activated esters. IB. Reactions of activated esters of amino acid and peptide derivatives with amines and amino acid esters. Helv Chim Acta 38, 83, 1955. 

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. 

The formation of tluorinated Q -hydroxy-jS-imino esters (180) by treatment of fluorinated imino ethers (179) with lithium 2,2,6,6-tetramethylpiperidide has been reported. A possible explanation for this interesting intramolecular rearrangement is proposed in Scheme 64. Acyclic imides derived from primary benzylic amines and amino acid esters have been found to undergo a novel nitrogen to carbon acyl migration via a base-generated carbanion to yield the corresponding a-amino... 

Oxidation of 2,6-di-te/ -but>l-4-phenylphenoI 20 in the presence of an amino acid ester as the nucleophile leads to the formation of amine protected amino acid derivatives. The protecting group is stable towards bases and can be removed ei-... 

Another possible mechanism for the racemization of amino acid esters involves the in situ, transient, formation of Schiff s bases by reaction of the amine group of an amino acid ester with an aldehyde. Using this approach, DKR of the methyl esters of proline 5 and pipecolic acid 6 was achieved using lipase A from C. ant-arclica as the enantioselective hydrolytic enzyme and acetaldehyde as the racemiz-ing agent (Scheme 2.4). Interestingly, the acetaldehyde was released in situ from vinyl butanoate, which acted as the acyl donor, in the presence of triethylamine. The use of other reaction additives was also investigated. Yields of up to 97% and up to 97% e.e. were obtained [6]. 

Lipo-amino acid derivatives are readily obtained in good yields by direct alkylation of amino acids esters with the related alkyl halides, e.g. farnesyl bromide, under careful control of the reaction conditions to avoid exhaustive alkylation of the amino group. 128 Alternatively, peptoid chemistry is applied for N-alkylation of glycine ester via reaction of alkyl amines, e.g. hexadecylamine, with ethyl bromoacetate. 36,98 ... 

The two main resin linkers developed so far are shown in Scheme 18, i.e. tris(alk-oxy)benzylamide- 412 and 4-alkoxybenzylamide-type linkers)341 the former being TFA labile and thus fully compatible with Fmoc/tBu and the latter strongly acid labile and correspondingly compatible with Boc/Bzl chemistry. As shown in the case of the tris(alk-oxy)benzaldehyde handle such handles may be introduced into the C-terminal amino acid ester by reductive amination, and after suitable N -protection coupled to amino-functionalized resins (see Scheme 18). Alternatively, the tris(alkoxy)benzaldehyde-functionalized resin, BAL resin, (see Scheme 14) is used to link the C-terminal amino acid ester by reductive amination. To overcome the difficult acylation of the V -arylamino acid ester derivative on resin (best results with 10 equivalent symmetrical anhydrides), synthesis in solution of the C-terminal dipeptide building block containing the amide handle followed by its attachment to the resin has been proposed)341 ... 

The enantioselective synthesis of the jS-amino acid ester shown in Figure 1.6 has recently been reported by Kubryk and Hansen (Merck) where good ees were obtained by asymmetric hydrogenation. Using an in-situ reaction with diBoc-anhydride to protect the amine group a crystalline product was obtained that was recrystallized to the required 99 % + ee purity very easily. 

Cleavage of amino acid esters occurs at both C— C bonds (a, b below) next to the nitrogen atom, loss of the carbalkoxy group being preferred (a). The aliphatic amine fragment decomposes further to give a peak at m/z 30. 

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