The design and synthesis of novel chiral Z-nitrones with applications towards the syntheses of enantiomerically pure 4-hydroxy amino acids

A number of 4-hydroxy amino acids have been synthesized via 1,3-dipolar cycloadditions of novel Z-nitrones and substituted olefins. Three achiral nitrones were synthesized in pursuit of a conformationally stable yet reactive Z-nitrone. The carboisopropoxynitrone was determined to be the best synthon in cycloadditions that favored a Z-nitrone oriented transition state. Solvent studies were performed for cycloaddition reactions and it was determined that polar solvents lead to "Z-derived" isoxazolidines whereas non-polar solvents primarily afford "E-derived" isoxazolidines. The incorporation of MgBr 2˙OEt2 to the reaction further enhanced the selectivity of the cycloaddition reaction in favor of "Z-derived" intermediates.;Chiral carboisopropoxynitrone derivatives were also realized and used in reactions with chiral olefins to afford optically active 4-hydroxy amino acids after several steps. (2R,4R)-4-hydroxyl-4-methylglutamic acid and (2R-4R)-monatin were both synthesized in high purity from corresponding optically active olefins and Z-nitrone. Furthermore, the (2S,4S) enantiomers of both amino acids could be synthesized via enantiomers of the chiral nitrone and olefins.