Dihydrooxazoles, stereoselective

Some further examples of stereoselective deprotonation/alkylation reactions of tricarbonyl-chromium complexed (V-methyl tetrahydroisoquinolines have been reported27. Starting with the enantiomerically pure (35)-methyl tetrahydroisoquinoline reaction with hexacarbonyl-chromium led to a mixture of endo- (40%) and exo- (60%) complexes, which were deprotonated with butyllithium and subsequently methylated with iodomethane. In this way methylation occurred firstly at the 4- and secondly at the 1-position. In all cases, the methyl group entered anti to the chromium complexed face. After separation of the alkylated complexes by chromatography and oxidative decomplexation, the enantiomerically pure diastereomers (—)-(l 5,35,47 )-and ( + )-(17 ,35,45)-1,2,3,4-tetrahydro-l,2,3,4-tetramethylisoquinolme were obtained, benzylic amines such as tetrahydroisoquinoline to 2-amino-4,5-dihydrooxazoles. Deprotona... 

While chiral 2-amino-4.5-dihydrooxazoles are not very successful as auxiliaries/precursors for the stereoselective alkylation of lithiated aliphatic amines28, they can be used effectively to obtain asymmetric induction in the alkylation of the a-position in benzylic amines. 

The chemistry of the oxazolidines, like the dihydrooxazoles, is characterized by reactions that take advantage of the opportunity for stereoselectivity. The chiral environment is often provided by the same amino alcohols, such as phenylglycinol or norephedrine, used to prepare dihydrooxazoles. 

The formation of 10 proceeded with total regio- and stereoselectivity, since cyclization occurs only from the /(-face, with the imidate nitrogen attacking the more substituted C-3 position. When the corresponding trichloroacetimidate was treated under the same conditions, a mixture of both the 4,5-dihydrooxazole and a 2-oxazolidinone were produced, the latter most probably arises from the hydrolysis of the 4,5-dihydrooxazole. 

Dihydrooxazoles are also effective ortho directors for nucleophilic addition to naphthalene and some heteroaromatic derivatives. Tandem additions result if the reaction mixtures are quenched with electrophiles (Scheme 54). When chiral oxazoles are used, asymmetric syntheses, such as that of scopadulcic acid, are achieved. Although most of the oxazoles employed have chelating groups to enhance stereoselectivity, the steric bias provided by valinol or t-leucinol derived oxazoles is often equivalent or superior. 

The chiral 2-alkyl-4,5-dihydrooxazole (12) is synthesized from (+)-(lS,2S)-l-phenyl-2-aminopropane-l,3-diol, the product of IiAlH4-reduction of phenylalanine (available from the chiral pool, see p. 160), and converted to the methyl ether 13 by alkylation with CHsI/NaH. As a result of internal asymmetric induction, the hthiation product of 13 occurs diastereoselectively and yields 14. In the case of 14 (R = Me, R = Et), hydrolysis transforms to the (+)-(S)-enantiomer of 2-methylbutanoic acid (15) as main product with moderate stereoselectivity ee = 67%) ... 

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