2-Oxazolidinone ring

A synthetically useful reductive cleavage of the 2-oxazolidinone ring has been utilized to give the cw-dimethylamino alcohol moiety, e.g., 7139. 

Kakeya, H., M. Morishita, H. Koshino et al. 1999. Cytoxazone A novel cytokine modulator containing a 2-oxazolidinone ring produced by streptomyces sp. J Org Chem 64 1052-1053. 

The reacting aldehyde displaces the oxazolidinone oxygen at the tetravalent boron in the reactive TS. The conformation of the addition TS for boron enolates is believed to have the oxazolidinone ring oriented with opposed dipoles of the ring and the aldehyde carbonyl groups. 

With titanium enolates it was found that use of excess (3 equiv.) of the titanium reagent reversed facial selectivity of oxazolidinone enolates.140 This was attributed to generation of a chelated TS in the presence of the excess Lewis acid. The chelation rotates the oxazolidinone ring and reverses the facial preference, while retaining the Z-configuration syn diastereoselectivity. 

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

Several new syntheses of the oxazolidinone ring have been published. Treatment of spoxyurethane 184 with a strong base induced the cyclisation to oxazolidinone 185 which, trough an olefine methathesis afforded 186 . Treatment with iron salt of acyl azide 187 afforded an aziridine, which, upon nucleophilic attack of a chloride ion, was transformed in the final oxazolidinone 188 <00CC287>. 

This class of rigid tricyclic fused oxazolidinones was synthesized in order to gain an understanding of the importance of the spatial relationship and torsional angle between the aryl and oxazolidinone rings with regard to antibacterial activity [51,65]. Considering the structure of an early lead compound,... 

Dup-721 (please see Fig. 2 for the structure), these tricyclic fused oxazolidinones have their aryl and oxazolidinone rings joined together by either one or two carbon linkers, resulting in the formation of the [6,5,5] and the... 

N-(2-Hydroxypropyl)carbamates (8.139, Fig. 8.13,b) are prodrugs that resemble the A-(2-hydroxyphenyl)carbamates discussed above. Here, activation yielded the tranquilizer mephenoxalone (8.140, Fig. 8.13,b) and an alcohol or a phenol such as paracetamol. Other active oxazolidinones could be obtained by replacing the MeO group in 8.139 (Fig. 8.13, b) with another substituent. For this series, the mechanism of activation is not an intramolecular nucleophilic attack, but, rather, decomposition of the deprotonated carbamate group as shown in Fig. 8.7,b, Reaction b, with the intermediate isocyanate being trapped to form the oxazolidinone ring. 

Metal complexes of bis(oxazoline) ligands are excellent catalysts for the enantioselective Diels-Alder reaction of cyclopentadiene and 3-acryloyl-l,3-oxa-zolidin-2-one. This reaction was most commonly utilized for initial investigation of the catalytic system. The selectivity in this reaction can be twofold. Approach of the dienophile (in this case, 3-acryloyl-l,3-oxazolidin-2-one) can be from the endo or exo face and the orientation of the oxazolidinone ring can lead to formation of either enantiomer R or S) on each face. The ideal catalyst would offer control over both of these factors leading to reaction at exclusively one face (endo or exo) and yielding exclusively one enantiomer. Corey and co-workers first experimented with the use of bis(oxazoline)-metal complexes as catalysts in the Diels-Alder reaction between cyclopentadiene 68 and 3-acryloyl-l,3-oxazolidin-2-one 69 the results are summarized in Table 9.7 (Fig. 9.20). For this reaction, 10 mol% of various iron(III)-phe-box 6 complexes were utilized at a reaction temperature of —50 °C for 2-15 h. The yields of cycloadducts were 85%. The best selectivities were observed when iron(III) chloride was used as the metal source and the reaction was stirred at —50 °C for 15 h. Under these conditions the facial selectivity was determined to be 99 1 (endo/exo) with an endo ee of 84%. 

As noted, direct acid- or base-catalyzed hydrolysis of the acyl C-N bond in the chiral alkylated 3-acyl-2-oxazolidinones is usually not practical. This is because it is often very slow and/or results in undesired side reactions such as cleavage of the oxazolidinone ring (there are, however, useful exceptions6 31-41). 

We added the acetylene to aldehyde 12 now because this step is not compatible with a protected guanidine. Treatment of 43 with EtMgBr to form the acetylide and addition of aldehyde 12 afforded 54% of 45 and 32% of 44. Under the basic conditions, the secondary amine adds to the carbamate to form the oxazolidinone ring. The decrease in the geminal coupling constant of the methylene hydrogens adjacent to the nitrogen from 11 Hz in 43 to 8 Hz in oxazolidinone 45 is characteristic of the... 

The Passerini-3CR between bifunctional 6-oxo-4-thiacarboxylic acids and alkyl-isocyanides, in the presence of a catalytic amount of tributylamine, afforded the tetracyclic structure 171, which included the 1,4-benzothioxepin group and an unexpected oxazolidinone ring, with formation of a rare orthoamide group (Scheme 2.62) [94]. 

Crich and coworkers used a mass spectral method to investigate the influence of the oxazolidinone ring and its. -acety I counterpart on the activation of sialyl donors [22], They found that a minimum cone voltage of 78 V is required to cause fragmentation of the glycosyl phosphate 76 under electrospray ionization conditions (Fig. 5.6). The comparable oxazolidinone phosphate (77) did not undergo mass spectral fragmentation... 

Other Oxazolidine as well as Thiazolidine Derivatives for Branching Amino Acids. The cyclic derivative of alanine and other amino acids employed most frequently for a-allq lation is not (1) but rather the benzaldehyde acetal (5), either with a benzoyl or with a Cbz group on nitrogen. These compounds were used for the preparation of 2-methyl-2-aminobutanoic acid, a-methylphenylalanine, a-methyllysine, 2-methylaspartic acid, and 2-methylglutamic acid. Bicyclic compounds containing oxazolidinone rings such as (6) (from alanine, leucine, and phenylalanine) and (7) (from azetidinecaiboxylic acid, proline, " hydroxyproline, and cysteine ) have also been applied to the synthesis of branched amino acids. 

Substituted oxazolidin-5-one derivatives, which are prepared from N -protected a-annino dicarboxyhc acids and paraformaldehyde, are employed for dual protection of the a-annino and a-carboxy groups in the synthesis of P-aspartyl and y-glutamyl esters (Scheme 4).Py For this purpose the oxazolidinone derivatives are synthesized by treatment of the Z amino acids with paraformaldehyde in a nnixture of acetic anhydride, acetic acid, and traces of thionyl chloride or by azeotropic distillation of the Z amino acids with paraformaldehyde and 4-toluenesulfonic acid in benzene. The resulting heterocychc compounds are readily converted into the tert-butyl esters with isobutene under acid catalysis. Esterification is achieved with tert-butyl bromidet or with Boc-F.P l Finally, the oxazolidinone ring is opened by alkaline hydrolysis or catalytic hydrogenolysis to yield the tert-butyl esters. 

The effect of the 4-substituent on the oxazolidinone ring was also examined. Results shown in Table 13-3 indicate that aromatic substituents provide the highest selectivities, and the diphenylmethyl (entry 1) and tritylmethyl auxiliaries (en-... 

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