2,2-Disubstituted Oxazolidines, New Chiral Auxiliaeies Based on the Conformational Control at the Amide Linkage.

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The 2,2-disubstituted oxazolidines bearing a chiral center at 4-position act as effective chiral auxiliaries with respect to the following points : 1) They are readily available in optically pure form from naturally occurring alpha-amino acids, 2) their alpha, beta-unsaturated amide derivatives are stabilized in Z-/s-cis conformers so that the unsaturated reaction cite is located close to the 4-shielding substituent, 3) such conformational stability is confirmed by the dynamic ^1H NMR spectra, 4) a nitrile oxide cycloaddition to the alpha, beta-unsaturated amide derivatives of 2,2-disubstituted oxazolidines shows the exclusive diastereofacial selectivity, 5) a cuprate conjugate addition to the alpha, beta-unsaturated amides is also absolutely diastereoselective, 6) the reactions affording the major stereoisomers occur at the diastereofaces opposite to the 4-substituent in their Z-/s-cis conformers, 7) the lithium Z-enolates derived from the oxazolidine amides undergo highly diastereoselective alkylations, 8) Michael additions using these lithium Z-enolate donors are also highly diastereoselective, 9) Z-/s-cis conformers again participate in these reactions, 10) these chiral auxiliaries are effective for asymmetric aldol reactions, 11) as a result, the 2,2-disubstituted oxazolidines act as excellent chirality-controlling auxiliaries in the reactions not only with nucleophiles (as alpha, beta-unsatutated amide derivatives) but also with electrophiles (as lithium Z-enolates).