Chiral naphthyloxazoline

The chiral naphthyloxazoline substrates can also be employed in asymmetric carbon-heteroatom bond-forming reactions with lithium amides, which provide unusual... 

The asymmetric addition of organolithium reagents to arylox azolines has been used to construct highly complex polycyclic terpene structures found in natural products. For example, the asymmetric addition of vinyllithium to chiral naphthyloxazoline 3 followed by treatment of the resulting anionic intermediate with iodoethyl dioxolane 61... 

The methodology was extended to an asymmetric introduction of snbstitnents to a naphthalene ring. When chiral naphthyloxazolines 13 were used as substrates, di- or trisubstituted dihydronaphthalenes 15 were obtained in high diastereomeric ratio (dr) after the treatment of intermediate azaenolate 14 with an electrophile (equation 7) °. Analogous reactions with a chiral naphthaldehyde imine were also reported . 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

The first use of chiral oxazolines as activating groups for nucleophilic additions to arenes was described by Meyers in 1984. " Reaction of naphthyloxazoline 3 with phenyllithium followed by alkylation of the resulting anion with iodomethane afforded dihydronaphthalene 10 in 99% yield as an 83 17 mixture of separable diastereomers. Reductive cleavage of 10 by sequential treatment with methyl fluorosulfonate, NaBKi, and aqueous oxalic acid afforded the corresponding enantiopure aldehyde 11 in 88% yield. 

An alternate route to chiral binaphthyls involves displacement of a chiral l-alkoxy group from an achiral naphthyloxazoline with a-naphthyllithium or an a-naphthyl Grignard reagent. The optical yields in this process depend on the choice of the leaving group. 

An asymmetric synthesis of chiral binaphthyls has been accomplished utilizing naphthyloxazolines. The method is based on the facile displacement of an o-methoxyl group in aryloxazolines by various nucleophiles (13). The aromatic substitution process has now also been found to proceed with o-methoxynaphthyloxazolines (Fig. 10). A number of nucleophilic reagents smoothly displaced the methoxyl group to and after hydrolysis led to 1-substituted-2-naphthoic acids Utilization of this efficient coupling... 

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