S - -5,5-Dimethyl-4-phenyl-2-oxazolidinone

Aldol Reactions of Ester Derivatives. The Titanium(IV) C/tlor/dc-catalyzed addition of aldehydes to 0-silyl ketene acetals derived from acetate and propionate esters proceeds with high stereoselectivity. Formation of the silyl ketene acetal was found to be essential for high diastereoselectivity. Treatment of the silyl ketene acetal, derived from deprotonation of the acetate ester with LICA in THF and silyl trapping, with a corresponding aldehyde in the presence of TiCU (1.1 equiv) afforded the addition products in 93 7 diastereoselectivity and moderate yield (51-67%). Similarly, the propionate ester provides the anti-aldol product in high antilsyn selectivity (14 1) and facial selectivity (eq 4). 

Nondestructive Removal of the Auxiliary. Primary alcohols are obtained by Lithium Aluminum Hydride reduction of the corresponding chiral esters. Also, hydrolysis of the auxiliary under basic conditions, 2N KOH in methanol, provides the carboxylic acid and recovered alcohol (3). 

Form Supplied in white crystalline solid commercially available. Analysis of Reagent Purity H NMR, C NMR, IR, GCMS, chiral HPLC. 

Preparative Methods the original literature reports that the desired 4-substituted-5,5-dimethyloxazolidin-2-one is readily accessible from the corresponding ct-amino acid via esterification (MeOH/SOCL) followed by Grignard addition to afford 

While this methodology is applicable to a variety of a-amino acids on a small scale, large-scale syntheses have proven problematic in that they are either low yielding or result in partial racemization of the desired auxiliary. In order to circumvent this difficulty, an alternative preparation has been developed (eq 2). Initially, an Af-Boc-a-amino acid methyl ester is reacted with an excess of methylmagnesium iodide to generate the corresponding tertiary alcohol. Subsequent cyclization into the desired 4-substituted-5,5-dimethyloxazolidin-2-one upon treatment with /er/-BuOK (eq 2) proceeds in good yield and with little or no racemization.  

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Experimental data showed that two successive developments with the same eluent [i.e., ethanol/water (80 20, v/v)] improved the resolution of cw-4,5-diphenyl-2-oxazolidinone ) = 0.77 (-I-) = 0.83, a = 1.46,/ s = 1-6]. The results reported in Table 4.6 confirmed that compounds having a benzyl or phenyl group in position 4 had a poor chance of enantiomeric discrimination. In fact, 4-benzyl-(a = 1.09), 4-benzyl-5,5-dimethyl- (a = 1.08), and 5,5-dimethyl-4-phenyl-2-oxazolidinone (a = 1.16) showed worse resolution than when the same aromatic group was present at position 5. Moreover, 4-methyl-5-phenyloxazolidin-2-one (a = 1.58) and, on MCTA column [26], 5-phenyl-2-oxazolidinone (a = 1.62) were baseline resolved. The behavior of cw-4,5-diphenyl-2-oxazolidinone was intermediate between the two aforementioned situations. 

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