3- Methyl-4-oxazolin-2-ones

A/-2-Methyl-2-(o-phenylazophenoxy)propionyl, 562 A/-4-Chlorobutyryl, 563 A/-Acetoacetyl, 563 A/-3-(p-Hydroxyphenyl)propionyl, 563 (A/ -Dithiobenzyloxycarbonylamino)acetyl, 563 A/-Acetylmethionine Derivative. 563 4,5-Diphenyl-3-oxazolin-2-one, 564... 

Once the oxazoline intermediate was formed, the reaction could undergo one of two paths or both - depending upon the type of substituent present in the 4-position of the phenylethylamine side chain. It was observed that when Ry was methyl or ethyl, the products obtained were from path A ... 

Fujisawa et al. [Ill] have reported that the magnesiiun complex prepared from chiral 2-[2-[(tolylsulfonyl)amino]phenyl]-4-phenyl-l,3-oxazoline 81 and methyl-magnesium iodide was efficient, in a stoechiometric amount, for promoting the enantioselective Diels-Alder reaction of 3-alkenoyl-l,3-oxazohdin-2-one with cyclopentadiene (Scheme 45) leading exclusively to the endo adducts in up to 92% ee. The use of 10 mol% of the complex led to an important decrease in enantioselectivity of the product (51% ee). 

Reports of [ 2 + 2] cycloaddition of nitrogen containing heterocycles to alkenes are so numerous that attention can be drawn here to only a few. Recent examples include the acetone-sensitized photoaddition of 4-oxazolin-2-one (248) to ethylene to give the cis-adduct 249,203 the photocycloadditions of N-substituted imidazoles to acrylonitrile204 and of N-methyl-4-hydroxy-quinol-2-one to cyclohexene,205 and the photoaddition of pentafluoro-pyridine to ethylene to give the 1 1- and 1 2-adducts 250 and 251,... 

Photoelimination of carbon dioxide from the 2-oxazolin-5-one 474 in the presence of methyl acrylate affords the cis- and frans-l-pyrrolines 475 and 476.394 A nitrile ylid is believed to be involved in this and other analogous transformations.395... 

The discovery of oxazoline hydroxamates as potential inhibitors of LpxC was the result of high-throughput screening of large libraries of compounds at the Merck Research Laboratories in collaboration with the Department of Biochemistry, Duke University Medical Center [95]. The lead compound, L-573,655, was a racemic mixture of 4-carbohydroxamido-2-phenyl-2-oxazoline, which had been previously made by Stammer et al. [96] as a precursor in the chemical synthesis of cyclosporine. Namely, (R,S)-serine methyl ester hydrochloride (149) is converted into (R,S)-4-carbomethoxy-2-phenyl-2-oxazoline (150) via treatment with ethyl benzimidate using the Elliot procedure [97]. Treatment of this ester with one equivalent each of hydroxylamine and sodium methoxide in methanol at room temperature affords the desired (R,S)-4-carbohydroxamido-2-phenyl-2-oxazoline (151), as depicted in Scheme 30. 

L-Serine methyl ester can be transformed into methyl oxazolidin-2-one-3-carboxylate with phosgene and aqueous potassium carbonate (90TL7407). Some AAs (Gly, Val, Phe) were transformed into their iV-(2-chloroethylcar-bamoyl) derivatives, and these can cyclize into oxazolines (Scheme 24) (83T2255). In boiling water they are transformed into hydantoin derivatives. 

The reaction of ketoximes 235 with dimethyl carbonate in the presence of K2CO3, carried out in an autoclave at 180-190 °C, afforded 3-methyl-4,5-disubstituted 4-oxazolin-2-ones 236 (equation 102). The formation of compounds 236 occurred via [3,3]sigma-tropic rearrangement of intermediates of the oxime methylated with dimethyl carbonate. 

Proton abstraction and epimerization of activated oxazolines is comparable to a similar epimerization known for oxazolidinones. For example, Omura and Smith reported an elegant synthesis of all four stereoisomers of 3-hydroxyleucine from ( )-4-methyl-2-penten-l-ol (Scheme 8.123). One of the key steps was the efficient epimerization of the cis-oxazolidinone ester 380 to the trans-oxazohdinone acid 381 during saponihcation. 

Many examples of the use of chiral Ca-symmetric bis(oxazoline) hgands have been presented here. Other examples include their use in various heteroannulations, one of which is shown in Figure 9.69. Here, the vinyl iodide, (Z)-3-iodo-2-methyl-2-propen-l-ol, 235 is condensed with 1,2-undecadiene to form the 3-methylene-2//-pyran derivative 237. " When this reaction was mn in the presence of 10 mol% of bis(oxazoline) Ugand 236 complexed with palladium(ll), 237 was produced in 70% yield with 79% ee. 

For (c), a macromonomer that has a pendant group accustomed to the solvent is used as a comonomer in the dispersion polymerization of a monomer that composes the particle. The surface of resulting particles is covered with the pendant group and consequently stabilized by a steric stabilization effect (14,15). In this sense the macromonomer is a kind of stabilizer that shows its effect through polymerization, and it could be called as a stabilizer formed in situ. A copolymer of macromonomer and particle-composing monomer, which joins the polymer particle, is much more effective for dispersion than a soluble stabilizer. With the dispersion polymerization of methyl methacrylate, which uses a macromonomer composed of an oligo-oxazoline pendant group, it is possible to cut the amount of stabilizer used to one-tenth or less compared to the oxazoline homopolymer stabilizer (16). 

Masked chiral a-hetero substituted carboxylic acid enolates have also shown utility in dia-stereoselective additions to nitroalkenes. For example, derivatives of a-hydroxycarboxylic acids, e.g. l,3-dioxolan-4-ones (187) a-amino acids, e.g. 1,3-imidazolidin-4-ones (188) and a-amino-fi-hydroxy-carboxylic acids, e.g. methyl 1,3-oxazolidin-4-carboxylates (189) and methyl l,3-oxazolin-4-carboxy-lates (190), have been employed.1S0a Further, diastereoselective additions of chiral (3-hydroxyesters (191), via the enediolates, to nitroalkenes (40) afford predominant anr/ -P-hydroxyesters (192 Scheme... 

The methylene bridge in the fused oxazoline (203), 6-methyl-2//,6//-oxazolo[5,4,3-j/]quinolin-4-one, shows great stability towards acid cleavage, such as heating in 47% hydriodic acid. It is cleaved by oxidation, however, when treated with activated manganese dioxide in acetic acid (73JA5003). 

Electrophilic substitution. A number of chiral nucleophilic species have been described that result in optically active a-alkyl aldehydes, ketones, acids, and acid derivatives upon alkylation and (usually) subsequent hydrolytic cleavage. Enders provides a number of examples (Figure 3) one of which results in the ant alarm pheromone, 4-methyl 3-heptanone (26 2 7). Studies by A. I. Meyers of the chemistry of anions of chiral oxazolines (Figure 4) were the first of the genre, however ( 8 ). Related reactions of chiral anions of metalloenamines and hydrazones (29, 30, 31) have in common with the alkylation of oxazolines metallated azaenolate intermediates that predispose one face of an azaenolate double bond to reaction with the electrophile. 

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