Phenyl-2-oxazolidinone

Equation (16) was tested against some data obtained for (R) 4-phenyl-2-oxazolidinone using a range of mixtures of ethanol, acetonitrile and -hexane as the mobile phase. The column chosen was similar to that previously used for the separation of the 4-phenyl-2-oxazolidinone which was 25 cm long, 4.6 mm I.D. packed with 5 mm silica particles bonded with the stationary phase Vancomycin. The results obtained are shown in Table 1 and this is the data used in subsequent computer calculations. 

Table. 1 Retention Volume of (R) 4-Phenyl-2-oxazolidinone Determined at Different Solvent Compositions...

Figure 20. Calculated Retention Volume of 4-Phenyl-2-oxazolidinone Plotted against Those Experimentally Determined...

Figure 22. A 3-D Set of Curves Relating the Separation Ratio of the Two Enantiomers of 4-Phenyl-2-oxazolidinone to the Composition of a Ternary Solvent Mixture...

The data from the separation of the enantiomers of 4-phenyl-2-oxazolidinone [14] gave an expression for the retention volume of the two enantiomers, which are reiterated as follows. 

The products of the conjugate addidon of W -4-phenyl-2-oxazolidinone to nitroalkenes at converted into o-ct-amino acids v/ith high enandomeric purity fEq 4 30 ... 

Phenyl-2-oxazolidinone was purchased from Sigma-Aldrich or Urquima, S.A. Amau de Vilanove, Barcelona, Spain and used as received. 

The conjugate addition of (R)- or (5)-4-phenyl-2-oxazolidinone to nitroalkenes is catalyzed by t-BuOK at -78 °C to give the addition product with excellent diastereoselectivity, the products are converted into vicinal diamines (Eq. 4.28).34... 

The products of the conjugate addition of (f )-4-phenyl-2-oxazolidinone to nitroalkenes are converted into D-a-amino acids with high enantiomeric purity (Eq. 4.30).36... 

Nicolas, E., Russell, K. C., and Hruby, V. J. (1993). Asymmetric 1,4-addition of organo-cuprates to chiral a, b-unsaturated N-Acyl-4-phenyl-2-oxazolidinones A new approach to the synthesis of chiral b-branched carboxylic acids. J. Org. Chem. 58, 766—770. 

S)-3- (3S,4R)-4-(3,4-dimethoxypheny[)-t-metkyl-2-oxo-3-azetidiny[ -4-phenyl-2-oxazolidinone yield ... 

A,4/ )-4-(3,4-Dimethoxyphenyl)-l,3-[Pg.800]

Section A.5). Indeed, three enantiomeric pairs of 2-oxazolidinones have been commercially available since 1991. Enantiomerically pure 4-phenyl-2-oxazolidinone has likewise been prepared from / -aminobenzeneethanol (phenylglycinol)64. Base-catalyzed acylation of the enantiomerically pure 2-oxazolidinones with an appropriate acyl chloride gives the desired 3-acyl-2-oxazolidinones 3, 6 and 9 which have been used extensively in highly diastereoselective reactions of various types such as alkylations, aldol reactions (see Section D.l.3.4.2.4), hydrox-ylations (see Section D.4.1), aminations (see Section D.7.1) and Diels-Alder reactions (see Section D. 1.6.1.6) alkylation giving products with induced chirality in the a-position. 

R1 = CH3 R2 — C6H5 R3 = C3H7 (4R,5S)-4-methy/-3-(1-oxopentyI)-5-phenyl-2-oxazolidinone yield 90%12... 

Table 11. (4R,5,S)-3-(2-Alkyl-l-oxoalkyl)-4-methyl-5-phenyl-2-oxazolidinones by Alkylation of the Enolates from (4R,5,S)-3-Acyl-4-methyl-5-phenyl-2-oxazolidinones...

Similarly, photolysis of chromium complex (CO)5Cr=C(OMe)(c-Pr) in the presence of two equivalents of the optically active 3-ethenyl-6(S)-phenyl-2-oxazolidinone under 90 psi CO pressure produced in high regio- and diastereo-selectively the 3-oxazolidine-substitued (2i ,3S)-cyclobutanone, in optical purity of > 97% de (equation 75)148. 

The iodine-catalyzed reaction of aziridines with carbon dioxide leads to 2-oxazolidinones (251). Because carbon dioxide effectively polymerizes ethyleneimine, only low yields are obtained when unsubstituted ethyleneimine reacts with C02. However, direct insertion of carbon dioxide [124-58-9] into aziridines can be accomplished, with better yields, by ethoxycarbonylation of aziridines with subsequent elimination of ethylene under flash vacuum conditions (252). 1- Phenyl aziridine [696-18-4] can react with C02 under antimony [7440-56-0] catalysis to give AI-phenyl-2-oxazolidinone in good yields (253). At low temperatures and with the exclusion of atmospheric humidity, the reaction of ethyleneimine with carbon dioxide produces the unstable ethyleneiminium salt [51645-58-2] of IV-vinylcarbamic acid (254,255). 

S)-Phenyl-2-oxazolidinone.6 A one-pot route to this chiral auxiliary involves reduction of L-phenylglycine and BF3 etherate in DME with borane-dimethyl sulfide complex at a temperature maintained at 82°. The resulting phenylglycinol is then treated with trichloromethyl chloroformate (or the more expensive triphosgene). 

Schering-Plough uses (S)-4-phenyl-2-oxazolidinone in the large-scale production of their cholesterol absorption inhibitor Zetia (ezetimibe) (11) (Scheme 23.l).40 2 Condensation of the alcohol 12 with imine 13 in the presence of a Lewis acid such as TiCl4 and tertiary amine base yields compound 14. Silylation followed by intramolecular cyclization with tetrabutylammonium fluoride (TBAF) yields the protected ezetimibe 15. Removal of the protecting groups is carried out with weak acid to afford Ezetimibe (11). 

CijH-nBrOu 1050-93-7) see Desoxiinetasone [4.S -[3(2R, 3.S ),4oc,5ocl]-3-(2-bromo-3-hydroxy-l-oxo-3-phenylpropyl)-4-methyl-S-phenyl-2-oxazolidinone (C H BrN04 144704-63-2) see Docetaxcl... 

Trimethylacetyl chloride (0.065 mol) was added to 4-methyl-2-pentenoic acid (0.06 mol) and triethylamine (0.187 mol) dissolved in 200 ml THF at —20°C. After 1 hour the mixture was treated with LiCl (0.55 mol) and (R)-(-)-4-phenyl-2-oxazolidinone (0.05 mol) and a thick suspension formed, which was stirred 20 hours at ambient temperature. The suspension was filtered and the filtrate concentrated. The residue was recrystallized using hexane/EtOAc, 5 1, and the product isolated in 68% yield as a white solid. 

The 4-phenyl-2-oxazolidinone auxiliary has also been employed in the TiCl4-mediated conjugate additions of allylsi-lanes (eq 58). Analogous reactions using the phenylalanine-derived auxiliary with dimethylaluminum chloride afforded lower selectivities. In these reactions the oxazolidinones perform better than the sultams. 

---