DEVELOPMENT OF METHODS FOR THE SYNTHESIS OF CHIRAL, HIGHLY FUNCTIONALIZED 2-AMINO-4-ARYL-4H-PYRANS

The development of new methods for the asymmetric synthesis of highly functionalized 2-amino-4-aryl-4H-pyrans is described. Two alternative synthetic routes: the 1,4-conjugate addition of chiral beta-ketoesters 3 or the N-acetoacetyl sultam 11 to arylidenemalononitriles 6, and the Michael addition of malononitrile to enantiomerically pure alpha-acetylcinnamates 5, have been designed. Depending upon the chiral auxiliary, the resulting 4H-pyrans were obtained in low [(-)-menthol, (-)-borneol, (-)-ethyl lactate] to good (Oppolzer's sultam) diastereomeric excesses. The absolute configuration at the new stereocenter in the minor isomer of compound 12a was determined as S by X-ray diffraction analysis. Reductive cleavage of 4H-pyrans 12 with lithium aluminium hydride yielded the enantiomerically pure or enriched alcohols 14.