Regioselective synthesis of nitrones by decarboxylative oxidation of N-alkyl-alpha-amino acids and application to the synthesis of 1-azabicyclic alkaloids

Tungstate-catalyzed oxidation of N-alkyl-alpha-amino acids with 30% H2O2 so lution under phase-transfer conditions gives nitrones regioselectively in g ood yields. Using this method, stereodivergent synthesis of (R)- and (S)-4- (t-butyldimethylsilyloxy)-1-pyrroline N-oxides ((R)-17a and (S)-17a) was ac hieved. In addition, (R)- and (S)-3-(t-butyldimethylsilyloxy)-1-pyrroline N -oxides ((R)-45 and (S)-45) were prepared by catalytic oxidation of the cor responding chiral pyrrolidines in a regioselective manner. These chiral cyc lic nitrones, 17 and 45 are versatile intermediates for the synthesis of op tically active nitrogen heterocycles, since stereoselective additions of ca rbon nucleophiles to these chiral nitrones can be readily performed. Typica lly, ZnI2-mediated addition of ketene t-butyldimethylsilyl methyl acetal (2 9a to (R)-17a gave the cis-adduct, methyl (2R,4R)-[1,4-bis(t-butyldimethyls ilyloxy)pyrrolidin-2-yl]acetate (cis-30). In contrast, the addition of lith ium acetylides 34 to the nitrone (R)-17a gave the trans-adducts, (2S,4R)-2- (1 alkynyl)-4- (t-butyldimethylsilyloxy)-1-hydroxypyrrolidines trans-35. Th ese adducts are useful intermediates for syntheses of the nitrogen heterocy cles (3R,5R)-1-aza-3-hydroxybicyclo[3.3.0]octane (37) and (6R,8R)-1-aza-8-h ydroxybicyclo[4.3.0]nonane (38), respectively. The ZnI2-mediated addition o f ketene silyl acetal 29a to the nitrone (R)-45 gave methyl (2S,3R)-[1,3-bi s(t-butyldimethylsilyloxy)pyrrolidin-2-yl]acetate (trans-50a), which was us ed for asymmetric synthesis of the Geissman-Waiss lactone ((-)-49).