Ester p-hydroxy-a-amino

Cydization of P-hydroxy-a-amino esters under Mitsunobu reaction conditions is an alternative approach to aziridine-2-carboxylic esters [6b, 13-16], In this case the P-hydroxy group is activated by a phosphorus reagent. Treatment of Boc-a-Me-D-Ser-OMe 13 (Scheme 3.5) with triphenylphosphine and diethyl azodicarboxylate (DEAD), for example, gave a-methyl aziridinecarboxylic acid methyl ester 14 in 85% yield [15]. In addition to PPh3/DEAD [13b, 15], several other reagent combi-... 

Mechanistic investigations revealed the intervention of a highly stereoselective retro aldol reaction, which could be minimized by using a catalytic amount of 1% NaOH aqueous solution and ammonium chloride, leading in turn to the establishment of a general and practical chemical process for the synthesis of optically active anti-P-hydroxy-a-amino esters 78 (Table 5.13) [41b],... 

Recently, Corey and coworkers prepared the cinchonidine-derived bifluoride 20 from the corresponding bromide by passage of a methanolic solution through a column of Amberlyst A-26 OH- form, and subsequent neutralization with 2 equiv. of 1 N HF solution and evaporation (the modified method C in Scheme 9.5). The catalytic activity and chiral efficiency of 20 (dried over P205 under vacuum) have been demonstrated by the development of a Mukaiyama-type aldol reaction of ketene silyl acetal 21 with aldehydes under mild conditions, giving mostly syw-P-hydroxy-a-amino esters 22 as the major diastereomer with good to excellent enantiomeric excesses (Table 9.4) [23],... 

A facile phase-transfer catalysis protocol was reported for the conversion of p-hydroxy-a-amino esters into enantiomerically pure /V-tosyl aziridine-2-carboxylates <07TL6509>. Utilization of the same methodology allowed for preparation of an aziridine carboxamide in essentially quantitative yield. 

Aldol-type reaction of the trimethylsilyl-t-butyl keteneacetal of A-diphenylmethyl-eneglycine with aldehydes in the presence of an Af-anthracen-Q-ylmethyl-O-benz.ylcin-chonidinium salt leads predominantly to (25,3/ )-P-hydroxy-a-amino esters. 

The diastereoselective synthesis of p-hydroxy-a-amino esters 200 and 201 has been achieved. Use of a chiral auxiliary on the enolate component leads to good a ri-selectivity, but in the absence of this additional vehicle for stereocontrol, both syn and anti isomers 202 were produced (Scheme 42). ... 

Scheme 12.11 Asymmetric phase-transfer catalytic aldol condensation of glycine imine ester 6Sa with aldehyde and its application to the synthesis of p-hydroxy-a-amino ester 85.

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. 

LLB, LiOH, and H2O promoted the direct aldol reaction of glycinate Schiff bases 12 with aldehydes 3, providing access to p-hydroxy-a-amino acid esters 13 (Scheme 4,bottom) [7],... 

The gold(I) complex is prepared in situ by the reaction of (1) with bis(cyclohexyl isocyanide)gold(I) tetrafluoroborate (2), typically in anhydrous dichloromethane. The dihydrooxazolines obtained provide a ready access to enantiomerically pure p-hydroxy-a-amino acid derivatives. High diastereo- and enantios-electivity are generally maintained with a wide variety of substituted aldehydes, and a-isocyanoacetate esters. N,N-Dimethyl-a-isocyanoacetamides and a-keto esters have been substituted for the a-isocyanoacetate ester and aldehyde component, respectively, sometimes with improved stereoselectivity. The effect of both the central and planar chirality of (1) on the diastereo- and enantioselectivity of the gold(I)-catalyzed aldol reaction has been studied. The modification of the terminal di-alkylamino group of (1) can lead to improvements in the stereos-... 

Shiori and co-workers used 5-substituted 4-oxazolecarboxylic acid esters 379 as p-hydroxy-a-amino acid synthons. They described a straightforward synthesis of 379 by acylation of an isocyanoacetic acid ester with an a-alkoxyacid 378 in the presence of diphenylphosphorylazide (DPPA) or diethylphosphoryl cyanide (DPPC) followed by base-catalyzed cyclization (Scheme 1.104). The reaction conditions do not epimerize optically active a-alkoxyacids. Dilute acid hydrolysis of 379 and reaction with (600)2 affords the protected aminotetronic acids 380. Stereoselective hydrogenation of 380 then yields the 1,4-lactones 381, key intermediates in the synthesis of amino sugars. A variety of a-alkoxyacids were studied, and some examples are shown in Table 1.30. 

Ring-opening of aziridinecarboxylic acids has been used in the conversion of threonine into /Areo-3-methylcysteine and in the synthesis of p-alkoxy-a-amino-acids. Improved methods have appeared for the synthesis of iV-(phosphono-acetyl)-amino-acids and for the preparation of y-esters of glutamic acid and (3-esters of aspartic acid. The protected P-hydroxy-a-amino-acids (278) are converted into a-fluoro-P-amino-acids (279) with DAST (Scheme 137). ... 

Figure 11.85 Diastereoselective synthesis of an e.p. (2R,3S)-p-hydroxy-a-amino[l,2- C2]-carboxylic acid from (2S)-f C2]BABS via a (2R,3R)-oxirane[l,2- C2lcarboxylic acid ester...

P-Eliminations. 3-Elimination of the hydroxy group of TV-protected p-hydroxy-a-amino acids has been effected using DSC and Triethylamine. Reaction of Z-threonine with equimolar DSC/EtyN in acetonitrile gave exclusively the (Z)-isomer of Z-DBut-OMe (eq 4). Similarly, use of a 1 2 molar ratio of DSC gave the (Z)-isomer of Boc-DBut-OSuc, which on treatment with the methyl ester of alanine gave Z-DBut-Ala-OMe (eq 5). 

After protection, the a-hydroxy esters can be reduced by DIBAL-H into O-protected a-hydroxyaldehydes that are very useful synthetic intermediates (e.g., leukotrienes,79 ionophore antibiotics,10 insect pheremones,11 etc.). The secondary hydroxyl group of the a-hydroxy esters may also be substituted with inversion of configuration after activation as triflates of nosylates (p-nitrobenzenesulfonates) to give a-alkyl esters12 or a-amino esters.13... 

In this development, both amino moieties are differentially protected and thus, incorporation of these amino acids into peptide chains either at the a- or p-position is possible. This procedure has also been applied to the synthesis of piperazine-2-carboxylic acids and derived peptides [135], Scheme 51. For example, the bicyclic a-hydroxy (S-lactam 161, upon ring expansion and subsequent coupling of the resulting NCA 162 with a-amino esters, affords 163 in good yield. 

OL, -Dehydroamino acids. N-Protected (Cbo and Boc) (3-hydroxy-a-amino acid esters (ethyl, benzyl) are converted into the corresponding a,p-dehydroamino acid derivatives by DAST and pyridine in CHiCl, at 0° (6.5-90% yield). The hydroxy group is probably converted into the —OSFiNlCiH,), derbative, which undergoes trans-e m -... 

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