2-Oxazolines chiral directing groups

Discussions of oxazolines as chiral directing groups are included in the previous sections under the appropriate reaction classifications. Meyers has already published a recent review of chiral oxazolines (1998) that focused primarily on their use in aromatic reactions and Ullmann coupling reactions in particular. The examples of oxazolines as chiral directing groups described in this section will include reactions that are not discussed in any previous section of this chapter. 

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... 

Scheme 3.17 Chiral oxazoline as an < r//w-lithiation directing group...

Directed ortho-metalation does not always occur with oxazoline compounds, as was shown by the chiral derivative 185 where competitive chelation of the n-butyllithium with the methoxy group prevented it from approaching close enough to abstract a proton from the benzene ring... 

Bidentate ferrocene ligands containing a chiral oxazoline substituent possess both planar chiral and center chiral elements and have attracted much interest as asymmetric catalysts.However, until recently, preparation of such compounds had been limited to resolution. In 1995, four groups simultaneously communicated their results on the asymmetric synthesis of these structures using an oxazoline-directed diastereoselective lithiation (Scheme 8.141). " When a chiral oxazolinylferrocene 439 was metalated with butyllithium and the resulting aryllithium species trapped with an electrophile, diastereomer 442 was favored over 443. The structure of the major diastereomer 442 was confirmed, either by conversion to a compound of known stereochemistry or by X-ray crystallography of the product itself or of the corresponding palladium complex. ... 

Novel chiral diaryl bis(oxazolines) with ethylene spacers between the aromatic ring and the oxazoline group, e.g., 63, are available by alkylation of the commercially available 2-methyl-2-oxazoline 62, while compounds in which the aromatic rings are directly attached to the oxazoline moiety, c.g., 64, were prepared by Ullmann coupling of bromoaryloxazolines <97S431>. 

The last group of chiral NHC ligand precursors is comprised of oxazoline-substituted imidazolium salts. The first derivative of this type 63 was reported by Herrmann et al. in 1998. A slight modification of the ligand backbone and use of the oxazoline C4 atom for bridging gave the imidazolium salt 64. The direct connection of the two heterocycles led to 65. Imidazolium salts built from oxazoline heterocycles like 66 were prepared by Glorius et alP ... 

A procedure for enantioselective synthesis of carboxylic acids is based on sequential alkylation of the anion of the oxazoline 9 via its lithium anion. Chelation by the methoxy group leads preferentially to the transition state in which the lithium is located as shown. The lithium acts as a Lewis acid in directing the approach of the alkyl halide. This is reinforced by a steric effect of the phenyl substituent. As a result, alkylation occurs predominantly from the lower face of the anion. The sequence in which the groups R and R are introduced determines the chirality of the product. The enantiomeric purity of disubstituted acetic acids obtained after hydrolysis is in the range of 70-90%. ... 

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