Oxazolidinones benzyl

What should the absolute sterechemistry of the oxazolidinone benzyl group of compound 1 be in order to furnish the required product 2 under the conditions reported ... 

The column was 25 cm long, 4.6 mm I.D. and packed with Partisil 10. It is seen that linear curves were obtained for three different solutes and two different moderators in n-heptane. Scott and Beesley [14] obtained retention data for the two enantiomers, (S) and (R) 4-benzyl-2-oxazolidinone. The column chosen was 25 cm long, 4.6 mm I.D. packed with 5 mm silica particles bonded with the stationary phase Vancomycin (Chirobiotic V provided by Advanced Separations Technology Inc., Whippany, New Jersey). This stationary phase is a macrocyclic glycopeptide Vancomycin that has a molecular weight of 1449.22, and an elemental composition of 54.69% carbon. 

Figure 19 Graph of Corrected Retention Volume of the (S) 4-Benzyl-2-oxazolidinone against the Reciprocal of the Volume Fraction of Ethanol...

The numerical constants were obtained over the temperature range of 5°C to 45°C and a concentration range of 0 to 0.5 volume fraction of ethanol inn-hexane.The effect of temperature and solvent composition on solute retention can, again, be best displayed by the use of 3-D graphs, and curves relating both temperature and solvent composition to the retention volume of the (S) enantiomer of 4-benzyl-2-oxazolidinone are shown in Figure 23. Figure 23 shows that the volume fraction of ethanol in the solvent mixture has the major impact on solute retention. 

Figure 5. Graphs of Retention Time of (R) 4-Benzyl-2-oxazolidinone against Temperature Program Rate for Three Different Initial Temperatures...

Scott and Beesley [2] measured the corrected retention volumes of the enantiomers of 4-benzyl-2-oxazolidinone employing hexane/ethanol mixtures as the mobile phase and correlated the corrected retention volume of each isomer to the reciprocal of the volume fraction of ethanol. The results they obtained at 25°C are shown in Figure 8. It is seen that the correlation is excellent and was equally so for four other temperatures that were examined. From the same experiments carried out at different absolute temperatures (T) and at different volume fractions of ethanol (c), the effect of temperature and mobile composition was identified using the equation for the free energy of distribution and the reciprocal relationship between the solvent composition and retention. 

In contrast, flash-vacuum pyrolysis (FVP)155 or spray-vacuum pyrolysis (SVP)154 of the homologous phenethyl azidoformates yield, in every instance except for the 4-cyano and 4-nitro-derivatives, the thermally stable [1,3]oxazino[3,4-a]azepines 9 accompanied by lesser amounts of the oxazolidinones 10, formed by nitrene insertion at the benzylic carbon center. 

The benzyl ester protecting group and oxazolidinone ring were hydrogeno-lyzed on 5% Pd/C in MeOH for 16 hours (Scheme 4.16).34... 

Benzotetramisole 213 has been identified as an effective catalyst for kinetic resolution of sec-benzylic and propargylic alcohols 214 to give 215 in excellent enantioselectivity O60L1351 06OL4859>. The benzotetramisole-catalyzed kinetic resolution has been extended to 2-oxazolidinone 217 via enantioselective /V-acylation <06JA6536>. 

Manabe and Ito have reported46 the use of Ar-benzyl-2,3-tra x-oxazolidinones as selective glycosyl donors for the synthesis of 1,2-czj glycosylic linkages. 

The chiral A/ -propionyl-2-oxazolidones (32 and 38) are also useful chiral auxiliaries in the enantioselective a-alkylation of carbonyl compounds, and it is interesting to observe that the sense of chirality transfer in the lithium enolate alkylation is opposite to that observed in the aldol condensation with boron enolates. Thus, whereas the lithium enolate of 37 (see Scheme 9.13) reacts with benzyl bromide to give predominantly the (2/ )-isomer 43a (ratio 43a 43b = 99.2 0.8), the dibutylboron enolate reacts with benzaldehyde to give the (3R, 25) aldol 44a (ratio 44a 44b = 99.7 0.3). The resultant (2R) and (25)-3-phenylpropionic acid derivatives obtained from the hydrolysis of the corresponding oxazolidinones indicated the compounds to be optically pure substances. 

In the reaction of the conformationally restricted epoxy alcohol 84 and methyl or benzyl isocyanate, the epoxy carbamate 85 was formed. Cycliza-tion of 85 in tetrahydrofuran in the presence of sodium hydride gave the oxazinone 86 in approximately 20% yield, and the oxazolidinone 87 (R = Me, CH2Ph) in 40-60% yield. The formation of the two products can be rationalized by different nucleophilic attacks on the urethane nitrogen. With increasing nucleophilicity of the nitrogen, the regioselectivity of the reaction is shifted toward the formation of 87 (92TL3009). 

Cycloaddition to 3-acryloyl-2,2-dialkyloxazolidines (35) proceeded in a highly stereoselective manner (Scheme 6.38) (191), but poorly so when 4-benzyl-5,5-dimethyl-2-oxazolidinone (36) was used as a chiral auxiliary (Scheme 6.39). 

Oxazolidinones have been prepared by participation of an N-benzyloxycarbonyl group with a leaving group on126-131 C-l or C-3 of a 2-amino-2-deoxyhexose,132-134 such as 3,4,6-tri-0-acetyl-2-(benzyl-... 

The final alkylation at N( ) of 39 was accomplished using alkyl halides and lithiated 4-benzyl-2-oxazolidinone as a base.30,31 The halides used for lV(5)-alkylation were also found suitable for /V(l (-alkylation, with the notable expansion to include other alkyl iodides beyond methyl and ethyl iodide. From the spectroscopic data of the final products 4, and in agreement with literature data in similar systems,30,31 no evidence was found for C-... 

For the final step involving functionalization at N( ) of 62, anilide deprotonation with lithiated 4-benzyl-2-oxazolidinone as a base and alkylation with benzyl bromides again proved effective. Compared to the results obtained in the benzodiazepine series, the N( 1 )-alkylation reaction was generally found to proceed less smoothly with the 3,4-disubstituted quinox-alinones 62. Good results were obtained only if the resin batches were submitted twice to the alkylation conditions. Figure 3.4 displays a selection of structures (63-65) accessible from this first synthetic approach. In no case was there any evidence for racemization at the a-carbon atom of the amino acid. 

Although the racemization of the a-carbon can now be considered a potential problem, the synthesis of 32-peptides has been achieved in the same way as seen for 33-peptides. As the 32-amino acids cannot be prepared from the analogous a-amino acids, Seebach and co-workers 5,7 opted to use Evans oxazolidinone chemistry to produce enantiomerically pure 32-amino acids. Alkylation of 3-acyloxazolidin-2-ones 17 with A-(chloromethyl)benzamide yielded the products 18 with diastereomeric ratios between 93 7 and 99 1 (Scheme 8). Removal of the chiral auxiliary (Li0H/H202) and debenzoylation (refluxing acid) was followed by ion-exchange chromatography to yield the free 32-amino acids 20 which were converted by standard means into Boc 21 or benzyl ester 22 derivatives for peptide synthesis. 

The y-amino-p-hydroxy acid derived oxazolidinones 55 are prepared from the corresponding N-unprotected y-amino-p-hydroxy ester derivatives by reaction with phosgene,1119,391 carbonyl diimidazole,[41] or benzyl chloroformate.[86] Alternatively, cyclization is obtained from the N-carbamate protected derivatives, i.e. from the TV-isopropenyloxycarbonyl derivatives under heating,[381 or from the TV-Boc or N-Z derivatives under basic conditions. [68 81 87] By analogy, the p,y-diamino acid analogue is converted into the imidazolidinone 57 by treatment of the unprotected compound with phosgene.[83 88]... 

The alcohol 177 was converted to starting substrates oxazolidinone 178 by acylation followed by reduction of the azide function along with cyclization. Oxazolidinone 178 was protected with f-butylpyrocarbonate-4-(dimethylamino) pyridine (DMAP) and triethylamine, which was further subjected to reductive cleavage of the benzyl ester unit to afford carboxylic acid 179. The treatment of 179 with solution of l-chloro-/V./V,2-trimethyl-1-propenv I airline resulted in the easy formation of the corresponding acid chloride which on reaction with imine in the presence of triethylamine provided the stereoselective formation of spiro-p-lactam 180. 

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