2-oxazoline system

Oxazoline Systems. The 2-oxazoline system has long been known42 and can readily be prepared43 from 2-aminoethanol derivatives and carboxylic acids. This compound has served as a potential precursor for elaborated car-... 

In conclusion, many chiral pyridine-based ligands have been prepared from the chiral pool and have been successfully tested as ligands for the copper- or rhodium-catalyzed cyclopropanation of olefins. Alfhough efficient systems have been described, sometimes leading interestingly to the major cis isomer, the enantioselectivities usually remained lower than those obtained with the copper-bis(oxazoline) system. 

In 2005 [61], Overman and coworkers described the application of their oxazoline system 41 to synthetically attractive trifluoroacetimidates 44 (Fig. 23) forming trifluoroacetamides 45, which, in contrast to benzamides 40, can be readily transferred into free primary allylic amines. 

Asymmetric reactions using chiral copper Lewis acids are also performed in aqueous media. It has been reported that an asymmetric Diels-Alder reaction proceeds smoothly in water using Cu(OTf)2 and abrine as a chiral ligand (Scheme 49).214 The Cu -bis(oxazoline) system is effective in asymmetric aldol reactions in an aqueous solvent such as water/ethanol and even in pure water.215... 

However, a more exciting application of this reaction is the oxazoline-directed synthesis of axially chiral biaryls. The oxazoline system not only activates the ortho-methoxy group for nucleophilic displacement but also determines the stereochemical outcome of the reaction. This provides a convenient method for the introduction of axial-chirality. Meyers group continues their earlier lead on this subject with reports of the stereoselective synthesis of tetrasubstituted biphenyls 391,392 examples are shown in Table 8.29 (Scheme 8.154). The best... 

Phthalimidopenicillin 21, which is not able to produce the oxazoline system, affords azetidinone 22 upon electrolysis in acidic media, and subsequent treatment of 22 with triethylamine gives the chlorinated azetidinone 23 in 70% overall yield (from 21, Scheme 2-7) 19>. 

Similar amidoester groups offered Meyers and coworkers new abilities, especially in asymmetric synthesis. The systems discussed here are 1,3-oxazolinic systems that are... 

Two final types of late metal zwitterions (see Figure 26) that have emerged very recently and appear to offer a good deal of promise as alternative catalysts are a P,A-substituted indenide system 26a and 26b,and a chiral, boron-bridged bis(oxazoline) system 26c.Future studies with these and other organometaiiic zwitterionic systems should elueidate the role of the zwitterion in fundamental transformations. 

A reasonable reaction mechanism may start with formation of a bromonium ion 3 by attack of NBS at the olefin, followed by oprening of 3 by the nitrile ( 4) and addition of water to the nitriUum ion 4. This sequence leads to bromoamides 5, which finally undergo Lewis acid-mediated ring-closure via SN2-type intramolecular O-alkylation of the amide function to render stereoselectively the oxazoline system of 2. 

Subsequent to this, other catalyst systems have been shown to give high enantioselectivities for unfunctionalised ketones, such as Ru-(phosphine-oxazoline) systems and a Rh-PennPhos catalyst in combination with KBr and 2,6-lutidine. ... 

Jew, Park, and coworkers extended the substrate scope of phase-transfer catalytic alkylation to the oxazoline system in order to synthesize chiral a-alkyl serine derivatives. The authors chose phenyl oxazoline derivative 74 [106] as the substrate (Scheme 12.6). In the presence of Cj-symmetric chiral quaternary ammonium bromide (S,S)-31c, the asymmetric phase-transfer alkylation of 74 with alkyl halides, followed by acidic hydrolysis, provided chiral a-alkyl serines in very high yields and enantioselecti vities. 

The mechanism of organolithium addition to naphthyl oxazolines is believed to occur via initial complexation of the alkyllithium reagent to the oxazoline nitrogen atom and the methyl ether to form chelated intermediate 17. Addition of the alkyl group to the arena 7t-system affords azaenolate 18, which undergoes reaction with an electrophile on the opposite face of the alkyl group to provide the observed product 4. The chelating methyl... 

More recent examples have employed a milder reagent system, triphenyl-phosphine and dibromotetrachloroethane to generate a bromo-oxazoline, which is subsequently dehydrohalogenated. Wipf and Lim utilized their method to transform intermediate 11 into the 2,4-disubstituted system of (+)-Hennoxazole k Subsequently, Morwick and coworkers reported a generalized approach to 2,4-disubstituted oxazoles from amino acids using a similar reagent combination, triphenylphosphine and hexachloroethane. ... 

In addition to a-additions to isocyanides, copper oxide-cyclohexyl isocyanide mixtures are catalysts for other reactions including olefin dimerization and oligomerization 121, 125, 126). They also catalyze pyrroline and oxazoline formation from isocyanides with a protonic a-hydrogen (e.g., PhCH2NC or EtOCOCHjNC) and olefins or ketones 130), and the formation of cyclopropanes from olefins and substituted chloromethanes 131). The same catalyst systems also catalyze Michael addition reactions 119a). 

From the several (not exhaustive) examples listed above, it is obvious that bis(oxazolines) associated to copper salts are efficient catalysts to perform Diels-Alder cycloadditions of numerous substrates, leading to highly valuable products with high diastereo- and enantioselectivity. Efforts have been moreover drawn towards the preparation of moisture- and air-stable systems... 

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