Several Ammonia Oxygen Acids Synthesis And Conformational Study

This thesis is focused on the asymmetric synthesis of a-aminoxy acids and p2-aminoxy acids and conformational studies of several kinds of aminoxy oligomers by NMR, IR, CD and X-ray analysis.An effective route for the synthesis of chiral a-aminoxy acids from unnatural resources—terminal alkynes and aldehydes—has been developed. The key step involves the asymmetric addition of terminal alkynes to aldehydes, catalyzed by N-methyl ephedrine/Zn(OTf)2. Then Mitsunobu reaction introduces the N-O group in high yield. The last step is the oxidation reaction that converts the alkyne triple bond to carboxylic acid group. The absolute configuration of the resultingα-aminoxy acid is determined by circular dichroism. Following this concise route, both (R) and (S)-aminoxy acid residues with a variety of side chains have been prepared in moderate overall yield (37-73%) and good ee value (up to 99%).Conformational studies of achiralα,α-disubstituted 2-aminoxy-2-methyl-propanic acid and aminoxy cyclopropane carboxylic acid (AOCC) have been carried out. While both residues induceαN-O turn formation in organic solvents and at solid state, the AOCC residue adopts a more rigid conformation. The secondary structures of a series of oligomers composed of AOCC and chiral a-aminoxy acid residues have been characterized by NMR, CD and X-ray analysis. The chiral residue induces the following AOCC residue to adoptαN-O turn conformation with the same handedness, but this effect decreases along the backbone (N→C) with the increase of the number of subsequent AOCC residues. In contrast, the chiral residue exerts no influence on the handedness of theαN-O turn structure of the preceeding AOCC residue.We have also made some progress on asymmetric synthesis and conformation studies ofβ2-aminoxy acid. For example, the simplestβ2-aminoxy acid, tert-butyl-2-(aminoxymethyl)propanoate was prepared from propionyl chloride in 6 steps. The sencondary structure of thisβ2-aminoxy acid monomer in organic solvents was characterized by NMR and IR analysis. A nine-membered ring intramolecular hydrogen bond was found between the C-terminal regular amide NH and the N-terminal carbonyl group, revealed by X-ray analysis. This secondary structure is consistent with the stable conformation obtained from the quantum mechanics calculation.