A-Bromo oxazolidinone

Oxazolidinones are the products of the acid-catalyzed condensation of a-hydroxyamides with aldehydes and ketones (equation 178). Tertiary amides derived from pyruvic acid undergo intramolecular cyclization when irradiated (equation 179) (78JOC419). Treatment of the a-bromo amide (308) with sodium hydride yields inter alia the dimeric oxazolidinone (309), presumably by way of an a-lactam, which adds to the carbonyl group of a second molecule of the amide (equation 180) (80JCS(P1)2249). 

Dehalogenation. The NBS-mediated radical side-chain bromination of (V,(V-di-ierf-butoxycarbonyl-protected phenylalanine, tyrosine, histidine, or tryptophan and subsequent treatment with AgNOs in acetone provide the frans-oxazolidinones predominantly, which are then converted to the 8-hydroxy amino acid derivatives in excellent overall yield. a-Bromo esters can be transformed to nitrate esters by treatment with AgNOs in acetonitrile. The subsequent oxidation with NaOAc/DMSO gives the corresponding glyoxylate esters. This strategy has been successfully applied into the total synthesis of macrocyclic (+)-brefeldin... 

A 3-acyl-4,5-unsubstituted-2(3//)-oxazolone 157 smoothly undergoes electrophilic addition with Br2 (or NBS) and PhSeCl in methanol to give frani-5-bromo-4-methoxy- and frani-4-methoxy-5-phenylselenenyl-2-oxazolidinones 158, respectively, with full regio- and trans-selectivity (Fig. 5.39). Both substituents thus... 

The (+)- and (—)-4,5-dialkoxy-2-oxazolidinones 173 and 174 prepared through the 5-bromo-4-methoxy- derivatives serve as reliable chiral synthons for the preparation of a wide variety of optically active a-amino acids 176 and a-amino aldehydes 177 (Fig. S.TS)." ... 

A camphor-based 3-acyl-2-oxazolidinone has also been used for diastereoselective alkylations66. The A-acylated auxiliary 18 is prepared in three steps from 7,7-dimethyl-2-oxobicy-clo[2.2.1]heptane-l-carboxylic acid (ketopinic acid, 17)67. Deprotonation by lithium diiso-propylamide in tetrahydrofuran at — 78 °C and subsequent alkylation with activated halides [(bromo- or (iodomethyl)benzene, 3-bromo- or 3-iodopropene] furnished moderate to good yields of alkylation products in high diastereomeric ratios (>97 3 by H NMR). With added hexamethylphosphoric triamide the alkylation yields are increased and bromoalkanes also give satisfactory yields. The diastereomeric ratios are, however, much lower (d.r. 70 30 to 85 15)67. 

Ytterbium trifluoromethanesulfonate promoted a radical atom-transfer addition of chiral 3-bromoacetyl-2-oxazolidinones to norbornadiene, which afforded the corresponding 5-ex<9-3-bromo-5-nortricycleneacetic acid derivatives in good yields and with high diastereoselectivity (90-96% de, when using the chiral 4-isopropyl- and 4-benzyl-substituted 2-oxazolidinone auxiliaries).133... 

RX. n-butyl bromide n-dodecanyl iodide cyclohexyl iodide ethyl bromo acetate methyl 2,3-di-O-acetyl-4-O-benzoyl-6-bromo-6-deoxy-ot-D-glucopyranoside methyl 2,3,4-tri-0-acetyl-6-deoxy-6-iodo-0 -D glucopyranoside l,2 3,4-di-0-isopropylidene-6-deoxy-6-iodo-a-D-galactopyranose methyl 2(R)-[(tert-butoxycarbonyl)amino]-3-iodo-propionate cyclic bis(trifluoromethyl)oxazolidinone bromide. 

Bio-Mega/Boehringer Ingelheim have used an oxazolidinone auxiliary in the synthesis of renin inhibitors (e.g., 40) for the treatment of hypertension and congestive heart failure.58 A multi-step derivitization of the oxazolidinone 41 from reaction of (6)-4-(l-methylethyl)-2-oxazolidinone and 4-bromo-4-pentenoic acid yielded the desired compound. 

Tetrahydro-l,3-oxazin-2-ones (368) can be obtained by the reaction of arylthiols with N-bromo-A-cinnamylcarbamates (367). Presumably a sulfenyl bromide, or its equivalent, is formed initially which then acts as an electrophilic agent to promote the cyclization step (Equation (44)). However, should sulfenyl chlorides be reacted with A-alkyl-A-cinnamylcarbamates (369) then the regioselectivity is changed and oxazolidinones (370) are formed instead (Equation (45)) <86JPR173>. 

Jamison synthesis of amphidinolide T1 started with the preparation of alkyne 201 via a diastereoselective propar-gylation using Evans chiral oxazolidinone auxihary and 3-bromo-l-phenyl-l-propyne [112] followed by the reduction of the diamide and protection of the resulting primary alcohol as a (er(-butyldimethylsilylether (Scheme 2.85). The latter was then engaged in the first transition metal-catalyzed reductive coupling in the presence of chiral epoxide 204 to... 

Stereoselective a-halogenation of enolates is an important approach for the generation of synthetically versatile, chiral building blocks. By use of an auxiliary approach, the acylated oxazolidinone derivatives developed by Evans have been showcased in diastereoselective enolate brominations (Scheme 3.33) [125]. Enolization of 226 (BujBOTf, amine base) and exposure of the boron enolate to NBS affords 228 in 95 5 dr. A key application of the bromo imides is their facile conversion into azides upon treatment with tetramethylguanidinium azide (229). The resulting azides such as 230 (dr=95 5) can readily be elaborated into chiral a-amino acids (see also Chapter 10). 

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